Advanced Solid TumorsPhase 1/2NCT03179436
Study of Quavonlimab (MK-1308) in Combination With Pembrolizumab (MK-3475) in Advanced Solid Tumors (MK-1308-001)
A Phase 1/2 study testing Quavonlimab, Pembrolizumab and Pembrolizumab/Quavonlimab in people with Advanced Solid Tumors, run by Merck Sharp & Dohme LLC at 53 sites in 16 countries.
Trial summary
This study will assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of escalating doses of quavonlimab when used in combination with pembrolizumab in participants with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- Quavonlimab, Pembrolizumab and Pembrolizumab/Quavonlimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 415 participants
- Where
- 53 sitesin 16 countries
- Study dates
- 2 Jul 2017to 8 Apr 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For Dose Escalation Phase:
- Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor (except NSCLC for Cohorts 2 and 3) by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit
- For Dose Confirmation Phase NSCLC Arms (A, B, C, and E):
- Have newly diagnosed histologically or cytologically-confirmed stage IIIB/stage IV NSCLC. Epidermal growth factor receptor (EGFR)-and anaplastic lymphoma kinase (ALK) translocation-directed therapy is not indicated as primary therapy. Participant must not have received prior systemic treatment for advanced NSCLC or must have received previous neoadjuvant and adjuvant chemotherapies ≥6 months before dosing of study drug if prior systemic treatment was given for early stage disease
- For Dose Confirmation Phase SCLC Arm (Arm D):
- Have histologically- or cytologically-confirmed metastatic (Stage III/IV) SCLC with progressive disease after ≥1 platinum-based chemotherapy regimen. Participants with platinum-sensitive disease are eligible
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- Have measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology
- Have Eastern Cooperative Oncology Group (ECOG) Performance Scale status of 0 or 1
- A female participant is eligible to participate if she is not pregnant or breastfeeding and at least 1 of the following conditions applies:
- Is not a woman of child bearing potential (WOCBP) OR
- Is a WOCBP and using a contraceptive method that is highly effective during the intervention period and for at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab, whichever comes last
- Female participants of childbearing potential must have negative urine or serum pregnancy test within 24 hours for urine and within 72 hours for serum prior to receiving the first dose of study treatment
- Male participants with a female partner(s) of child-bearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication and refrain from donating sperm during this period
- Must submit an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample)
- For Efficacy Expansion Phase Arms F and G:
- Have histologically/cytologically-confirmed unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer (AJCC) staging system version 8, not amenable to local therapy
- Have at least 1 measurable lesion by CT or MRI per RECIST 1.1 by BICR. Cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions
- Participants with unresectable Stage III or IV disease must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies (combinations with anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4] agents will not be allowed)
- Participants who receive anti-PD-1 therapy as adjuvant treatment following complete resection of Stage III or IV melanoma and have disease recurrence (unresectable loco-regional disease or distant metastases) while on active treatment or within 6 months of stopping anti-PD-1 are eligible
- Have submitted pre-trial imaging and provided a baseline tumor sample
- Proto-oncogene B-raf (BRAF) V600 mutation-positive melanoma participants should have received targeted therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) prior to enrolling on this study; however, they are not required to progress on this treatment prior to enrollment
- BRAF V600E mutation-positive melanoma participants who have NOT received a BRAF inhibitor (either as adjuvant therapy or in the metastatic disease setting) with lactate dehydrogenase (LDH) < local upper limit of normal (ULN), no clinically significant tumor-related symptoms, and absence of rapidly progressing metastatic melanoma. Approximately 10 participants each from Arms F and G will have 2 mandatory biopsies
- For Dose Coformulation Phase Arm I:
- Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for or refused all treatment known to confer clinical benefit
- Meet all requirements for Dose Escalation Phase and Dose Confirmation Phase
- For the Coformulation Phase - Arm K (China only):
- Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit
- Be a Chinese participant residing in China.
Who cannot join
- For all phases of the study: Has received previous treatment with another agent targeting cytotoxic T lymphocyte leukocyte antigen (CTLA)-4
- For Dose Confirmation Phase:
- Has received previous treatment with another agent targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
- Has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment
- Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of quavonlimab.
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- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
- For Dose Escalation Cohorts (1-3) and Dose Confirmation Arms (A-E):
- Has known untreated central nervous system (CNS) metastases. Has known carcinomatous meningitis
- Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse events (irAE)
- Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study drug
- Has any active infection requiring therapy
- Has a history of interstitial lung disease, history of noninfectious pneumonitis that required steroids (or has current pneumonitis), or history of inflammatory bowel disease
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
- Has clinically significant cardiac disease
- Has received a live or live attenuated vaccine within 28 days of planned treatment start
- Has known history of human immunodeficiency virus (HIV) and/or known active Hepatitis B or C infections, and/or known to be positive for hepatitis B surface antigen (HBsAg)/ hepatitis B virus (HBV) DNA
- Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with screening and for up to 120 days following cessation of pembrolizumab or pembrolizumab/quavonlimab
- Has not fully recovered from any effects of major surgery without significant detectable infection
- For Arm F and G (Efficacy Expansion Phase) and Arm K (Coformulation Phase) ONLY:
- Has known active CNS metastases and/or carcinomatous meningitis
- Has not had resolution of anti-PD-1 antibody-related AEs, including immune-mediated AEs back to Grade ≤1 or baseline (not applicable to Arm K)
- Has not discontinued steroid treatment for an irAE for at least 2 weeks prior to the first dose of study drug (not applicable to Arm K)
- Has ocular melanoma (not applicable to Arm K)
- Has mucosal melanoma (not applicable to Arm K)
- Has had an allogenic tissue/solid organ transplant
Trial locations and contacts
53 sites in 16 countries.
53 sites in 16 countries
Australia8 sites
Ballarat Health Services ( Site 0022)
Ballarat, Victoria, 3350
Blacktown Hospital. Western Sydney local health district ( Site 0009)
Blacktown, New South Wales, 2148
Gallipoli Medical Research Foundation-GMRF CTU ( Site 0019)
Brisbane, Queensland, 4120
Cairns and Hinterland Hospital and Health Service ( Site 0020)
Cairns, Queensland, 4870
Ashford Cancer Centre Research ( Site 0012)
Kurralta Park, South Australia, 5037
Alfred Health ( Site 0018)
Melbourne, Victoria, 3004
Calvary Mater Newcastle ( Site 0025)
Waratah, New South Wales, 2298
Melanoma Institute Australia ( Site 0017)
Wollstonecraft, New South Wales, 2065
United States5 sites
Inova Schar Cancer Institute ( Site 1001)
Fairfax, Virginia, 22031-4867
Banner MD Anderson Cancer Center ( Site 0013)
Gilbert, Arizona, 85234
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0005)
Hackensack, New Jersey, 07601
Tennessee Oncology Nashville ( Site 0004)
Nashville, Tennessee, 37203
South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001)
San Antonio, Texas, 78229
Canada5 sites
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 1102)
Montreal, Quebec, H2X 0A9
Jewish General Hospital ( Site 1105)
Montreal, Quebec, H3T 1E2
McGill University Health Centre ( Site 1101)
Montreal, Quebec, H4A 3J1
Sunnybrook Research Institute ( Site 1103)
Toronto, Ontario, M4N 3M5
Princess Margaret Cancer Centre ( Site 1104)
Toronto, Ontario, M5G 2M9
France5 sites
Institut Bergonie ( Site 3306)
Bordeaux, Gironde, 33076
CHRU Lille - Hopital Claude Huriez ( Site 3302)
Lille, Nord, 59037
Hopital La Timone ( Site 3303)
Marseille, Bouches-du-Rhone, 13005
CH Lyon Sud Hospices Civils de Lyon ( Site 3307)
Pierre-Bénite, Rhone, 69495
Gustave Roussy ( Site 3305)
Villejuif, Val-de-Marne, 94800
Spain5 sites
Hospital Clinic i Provincial de Barcelona ( Site 3401)
Barcelona, 08036
Onkologikoa - Instituto Oncologico de San Sebastian ( Site 3405)
Donostia / San Sebastian, Gipuzkoa, 20014
Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 3403)
L'Hospitalet de Llobregat, Barcelona, 08908
Hospital Universitario Virgen de la Macarena ( Site 3402)
Seville, 41009
Hospital General Universitario de Valencia ( Site 3404)
Valencia, Valenciana, Comunitat, 46014
South Korea4 sites
Asan Medical Center ( Site 0006)
Seoul, Seoul, 05505
Seoul National University Hospital ( Site 0007)
Seoul, 03080
Severance Hospital Yonsei University Health System ( Site 0008)
Seoul, 03722
Samsung Medical Center ( Site 0010)
Seoul, 06351
China3 sites
Beijing Cancer hospital-Digestive Oncology ( Site 5001)
Beijing, Beijing Municipality, 100142
Chongqing Cancer Hospital-Phase 1 Unite ( Site 5004)
Chongqing, Chongqing Municipality, 400030
Sir Run Run Shaw Hospital-Medical Oncology ( Site 5003)
Hangzhou, Zhejiang, 310016
Israel3 sites
Rambam Medical Center ( Site 0003)
Haifa, 3109601
Hadassah Ein Karem Hebrew University Medical Center ( Site 0021)
Jerusalem, 9112001
Sheba Medical Center - Cancer Center ( Site 0002)
Ramat Gan, 52621
Italy3 sites
Istituto Nazionale Tumori Fondazione Pascale ( Site 3903)
Naples, 80131
IRCCS Istituto Oncologico Veneto ( Site 3905)
Padova, 35128
Policlinico Le Scotte - A.O. Senese ( Site 3907)
Siena, 53100
South Africa3 sites
Sandton Oncology Medical Group PTY LTD ( Site 2701)
Johannesburg, Gauteng, 2196
Cape Town Oncology Trials Pty Ltd ( Site 2704)
Kraaifontein, Western Cape, 7570
Cancercare Rondebosch Oncology ( Site 2706)
Rondebosch, Western Cape, 7700
Japan2 sites
Hyogo Cancer Center ( Site 0015)
Akashi, Hyōgo, 673-8558
National Cancer Center Hospital East ( Site 0014)
Kashiwa, Chiba, 277-8577
New Zealand2 sites
Auckland City Hospital ( Site 0016)
Auckland, 1023
Canterbury District Health Board ( Site 0023)
Christchurch, Canterbury, 8011
Poland2 sites
Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 4803)
Poznan, Greater Poland Voivodeship, 60-780
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 4801
Warsaw, Masovian Voivodeship, 02-781
Chile1 site
Fundacion Arturo Lopez Perez ( Site 5601)
Santiago, Region M. de Santiago, 7500921
Greece1 site
Regional General Hospital of Athens "Laiko" ( Site 3001)
Athens, Attica, 115 27
Sweden1 site
Skanes Universitetssjukhus Lund. ( Site 4601)
Lund, Skåne County, 221 85
About this study
Official title: A Phase 1 / 2 Open Label, Multi-Arm, Multicenter Study of MK-1308 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
This study will assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of escalating doses of quavonlimab when used in combination with pembrolizumab in participants with advanced solid tumors.
Read the detailed description
After screening, participants will be assigned to the Dose Escalation, Dose Confirmation, Efficacy Expansion, or Coformulation Phase. The Dose Escalation Phase will evaluate available PK and safety data including dose limiting toxicities (DLTs). The Dose Confirmation Phase will gather additional safety, tolerability, PK, and preliminary efficacy data of quavonlimab in combination with pembrolizumab, and will include first-line advanced/metastatic non-small cell lung cancer (NSCLC) and second line (and beyond) advanced/metastatic small cell lung cancer (SCLC). The purpose of the Efficacy Expansion Phase is to gather preliminary anti-tumor efficacy data for quavonlimab in combination with pembrolizumab as well as for quavonlimab monotherapy in the specific target population of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) refractory melanoma. The Coformulation Phase will evaluate the safety and PK of a coformulated product of pembrolizumab/quavonlimab (MK-1308A) in comparison to that of the single, co-administered products given at the same dose and schedule, and include participants with advanced solid tumors and participants from mainland China.
- Conditions
- Advanced Solid Tumors
- Being tested
- Quavonlimab, Pembrolizumab, Pembrolizumab/Quavonlimab
- Keywords
- Programmed Cell Death Protein 1 (PD-1, PD1),, Programmed Cell Death Ligand 1 (PD-L1, PDL1), Programmed Cell Death Ligand 2 (PD-L2, PDL2)
- Medical subject headings
- Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QuavonlimabBiological
Also called MK-1308
Quavonlimab is administered intravenously (IV) during the Dose Escalation Phase and Dose Confirmation Phase at either DL1 or DL2, and is administered IV during the Efficacy Expansion Phase at DL2.
PembrolizumabBiological
Also called Keytruda®
Pembrolizumab is administered IV at PDL1 on Day 1 of each cycle starting Cycle 2 for the Dose Escalation Phase or starting Cycle 1 of the Dose Confirmation Phase. Pembrolizumab is administered IV at PDL2 on Day 1 of each cycle for the Efficacy Expansion Phase (Arm G).
Pembrolizumab/QuavonlimabDrug
Also called MK-1308A
Pembrolizumab/Quavonlimab is a coformulated product composed of quavonlimab at DL1 in combination with pembrolizumab at dose level 2 (PDL2).
| Study group | Role | What they receive |
|---|---|---|
| Escalation: Dose Level (DL) 1 Quavonlimab + Pembro: Cohort 1 | Experimental | On Cycle 1, Day 1 of the Dose Escalation Phase, advanced solid tumor participants receive a single monotherapy dose lead-in with quavonlimab at dose level 1 (DL1). On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL1 in combination with pembrolizumab (pembro) at pembrolizumab dose level 1 (PDL1) according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study. Receives: Biological: Quavonlimab; Biological: Pembrolizumab |
| Escalation: DL 2 Quavonlimab + Pembro: Cohort 2 | Experimental | On Cycle 1, Day 1 of the Dose Escalation Phase, participants with advanced solid tumors except NSCLC receive a single monotherapy dose lead-in with quavonlimab at DL2. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL2 in combination with pembrolizumab at PDL1 according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study. Receives: Biological: Quavonlimab; Biological: Pembrolizumab |
| Escalation: DL 3 Quavonlimab + Pembro: Cohort 3 | Experimental | On Cycle 1, Day 1 of the Dose Escalation Phase, participants with advanced solid tumors except NSCLC receive a single monotherapy dose lead-in with quavonlimab at DL3. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL3 in combination with pembrolizumab at PDL1 according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study. Receives: Biological: Quavonlimab; Biological: Pembrolizumab |
| Confirmation: DL 1 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm A | Experimental | On Cycle 1, Day 1 of the Dose Confirmation Phase and during all subsequent cycles, participants with NSCLC receive quavonlimab at DL1 in combination with pembrolizumab at PDL1, both according to Schedule 1. Participants will be treated for up to 35 cycles total on study. Receives: Biological: Quavonlimab; Biological: Pembrolizumab |
| Confirmation: DL 1 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm B | Experimental | On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with NSCLC receive quavonlimab at DL1 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and quavonlimab at DL1 according to Schedule 2. Participants will be treated for up to 35 cycles total on study. Receives: Biological: Quavonlimab; Biological: Pembrolizumab |
| Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm C | Experimental | On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with NSCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and at DL2 quavonlimab according to Schedule 2. Participants will be treated for up to 35 cycles total on study. Receives: Biological: Quavonlimab; Biological: Pembrolizumab |
| Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (SCLC): Arm D | Experimental | On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with SCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and quavonlimab at DL2 according to Schedule 2. Participants will be treated for up to 35 cycles total on study. Receives: Biological: Quavonlimab; Biological: Pembrolizumab |
| Confirmation: DL 2 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm E | Experimental | On Cycle 1, Day 1 of the Dose Confirmation Phase and during all subsequent cycles, participants with NSCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1 according to Schedule 1. Participants will be treated for up to 35 cycles total on study. Receives: Biological: Quavonlimab; Biological: Pembrolizumab |
| Expansion: DL1 Quavonlimab Schedule 2+PDL2 Pembro Schedule 2: Arm F | Experimental | On Cycle 1, Day 1 of the Efficacy Expansion Phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma receive quavonlimab at DL1 in combination with pembrolizumab at pembrolizumab dose level 2 (PDL2). Both quavonlimab and pembrolizumab will be administered according to Schedule 2 for up to 24 months on study. Receives: Biological: Quavonlimab; Biological: Pembrolizumab |
| Expansion: DL1 Quavonlimab Schedule 2 Monotherapy: Arm G | Experimental | On Cycle 1, Day 1 of the Efficacy Expansion Phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma receive quavonlimab at DL1 according to Schedule 2 for up to 24 months on study. Participants who demonstrate radiographically confirmed progressive disease in Arm G will be eligible to receive combination therapy with pembrolizumab (crossover). Receives: Biological: Quavonlimab |
| Coformulation: Pembrolizumab/Quavonlimab Schedule 2: Arm I | Experimental | On Cycle 1, Day 1 of the Coformulation Phase and during all subsequent cycles, participants with advanced/metastatic solid tumors receive pembrolizumab/quavonlimab according to Schedule 2 for up to 24 months on study. Receives: Drug: Pembrolizumab/Quavonlimab |
| Coformulation Phase in China: Pembrolizumab/Quavonlimab Schedule 2: Arm K | Experimental | On Cycle 1, Day 1 of the Coformulation Phase and during all subsequent cycles, participants in mainland China with advanced solid tumors receive pembrolizumab/quavonlimab according to Schedule 2 for up to 24 months on study. Receives: Drug: Pembrolizumab/Quavonlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT)
DLT was defined as toxicity that is possibly, probably, or definitely related to study therapy and may result in a change in the given dose. DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days (except thrombocytopenia); most non-hematologic AEs ≥ Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for >1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 or 3 of Dose Escalation or Cycle 2 of Dose Confirmation due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity.
Measured: Up to 6 weeks
Number of Participants With ≥1 Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who experienced an AE are presented.
Measured: Up to approximately 77 months
Number of Participants Discontinuing Study Treatment Due to an AE
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who discontinued study treatment due to an AE are presented.
Measured: Up to approximately 26 months
Efficacy Expansion: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) Based on Adjusted Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per adjusted Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR in the concurrent randomized subset as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, only data for arms F and G were presented for this endpoint.
Measured: Up to approximately 72 months
Secondary outcomes (10)
Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab
AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. AUC of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Measured: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Maximum Concentration (Cmax) of Pembrolizumab
Cmax was defined as the maximum concentration of pembrolizumab observed in plasma. Cmax determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. Cmax of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Measured: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Minimum Concentration (Cmin) of Pembrolizumab
Cmin was defined as the minimum or "trough" concentration of pembrolizumab observed after its administration and just prior to the administration of a subsequent dose. Cmin determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. Cmin of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3, Day 1 on Cycle 4. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Measured: At designated time points up to - Cohorts 1-3: Day 1 Cycle 4, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308)
AUC was defined as a measure of quavonlimab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. AUC of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Measured: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Maximum Concentration (Cmax) of Quavonlimab
Cmax was defined as the maximum concentration of quavonlimab observed in plasma. Cmax determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. Cmax of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Measured: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Minimum Concentration (Cmin) of Quavonlimab
Cmin was defined as the minimum or "trough" concentration of quavonlimab observed after its administration and just prior to the administration of a subsequent dose. Cmin determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. Cmin of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Measured: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs)
Non-Treatment emergent (TE) ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with pembrolizumab (i.e., at predose). Evaluable participants (used as the denominator for analysis) are the total number of negative, inconclusive, and positive participants (non-treatment emergent, treatment emergent and treatment boosted). Inconclusive participants are the number of participants with no positive ADA samples present and the drug concentration in the last sample above the drug tolerance level. ADA determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for arm G and cross over phase.
Measured: Cohorts 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycles 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days.
Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs)
Non-Treatment emergent (TE) ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with quavonlimab (i.e., at predose). Evaluable participants (used as the denominator for analysis) are the total number of negative, inconclusive, and positive participants (non-treatment emergent, treatment emergent and treatment boosted (TB)). Inconclusive participants are the number of participants with no positive ADA samples present and the drug concentration in the last sample above the drug tolerance level. ADA determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase.
Measured: Cohort 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycle 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, G, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days.
Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, no analysis was planned for the cross over phase.
Measured: Up to approximately 72 months
Efficacy Expansion: Duration of Response (DOR) as Assessed by BICR Based on Adjusted RECIST v1.1
DOR was defined as the time from first documented evidence of complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, only data for arms F and G were presented for this endpoint.
Measured: Up to approximately 72 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2017
- Study start2 Jul 2017
- Primary completion8 Apr 2024
- Study completion8 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 415 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03179436
- Sponsor's protocol ID
- 1308-001
- Other IDs
- MK-1308-001, 173820, 2019-003703-35, 2019
- Status last verified
- Mar 2025
- First submitted
- 31 May 2017
- Last updated
- 8 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Perets R, Bar J, Rasco DW, Ahn MJ, Yoh K, Kim DW, Nagrial A, Satouchi M, Lee DH, Spigel DR, Kotasek D, Gutierrez M, Niu J, Siddiqi S, Li X, Cyrus J, Chackerian A, Chain A, Altura RA, Cho BC. Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer. Ann Oncol. 2021 Mar;32(3):395-403. doi: 10.1016/j.annonc.2020.11.020. Epub 2020 Dec 2.
PubMed 33276076Cho BC, Yoh K, Perets R, Nagrial A, Spigel DR, Gutierrez M, Kim DW, Kotasek D, Rasco D, Niu J, Satouchi M, Ahn MJ, Lee DH, Maurice-Dror C, Siddiqi S, Ren Y, Altura RA, Bar J. Anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer. Lung Cancer. 2021 Sep;159:162-170. doi: 10.1016/j.lungcan.2021.07.009. Epub 2021 Jul 18.
PubMed 34371366
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 / 2 Open Label, Multi-Arm, Multicenter Study of MK-1308 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03179436
- Acronym / sponsor ID
- 1308-001
- Conditions
- Advanced Solid Tumors
- Keywords
- Programmed Cell Death Protein 1 (PD-1, PD1),, Programmed Cell Death Ligand 1 (PD-L1, PDL1), Programmed Cell Death Ligand 2 (PD-L2, PDL2)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 415 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 2 Jul 2017 (actual)
- Primary completion
- 8 Apr 2024 (actual)
- Study completion
- 8 Apr 2024 (actual)
- First posted
- 7 Jun 2017 (actual)
- Results
- Posted 8 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of escalating doses of quavonlimab when used in combination with pembrolizumab in participants with advanced solid tumors.
Detailed description
After screening, participants will be assigned to the Dose Escalation, Dose Confirmation, Efficacy Expansion, or Coformulation Phase. The Dose Escalation Phase will evaluate available PK and safety data including dose limiting toxicities (DLTs). The Dose Confirmation Phase will gather additional safety, tolerability, PK, and preliminary efficacy data of quavonlimab in combination with pembrolizumab, and will include first-line advanced/metastatic non-small cell lung cancer (NSCLC) and second line (and beyond) advanced/metastatic small cell lung cancer (SCLC). The purpose of the Efficacy Expansion Phase is to gather preliminary anti-tumor efficacy data for quavonlimab in combination with pembrolizumab as well as for quavonlimab monotherapy in the specific target population of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) refractory melanoma. The Coformulation Phase will evaluate the safety and PK of a coformulated product of pembrolizumab/quavonlimab (MK-1308A) in comparison to that of the single, co-administered products given at the same dose and schedule, and include participants with advanced solid tumors and participants from mainland China.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Escalation: Dose Level (DL) 1 Quavonlimab + Pembro: Cohort 1 | Experimental | Biological: Quavonlimab, Biological: PembrolizumabOn Cycle 1, Day 1 of the Dose Escalation Phase, advanced solid tumor participants receive a single monotherapy dose lead-in with quavonlimab at dose level 1 (DL1). On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL1 in combination with pembrolizumab (pembro) at pembrolizumab dose level 1 (PDL1) according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study. |
| Escalation: DL 2 Quavonlimab + Pembro: Cohort 2 | Experimental | Biological: Quavonlimab, Biological: PembrolizumabOn Cycle 1, Day 1 of the Dose Escalation Phase, participants with advanced solid tumors except NSCLC receive a single monotherapy dose lead-in with quavonlimab at DL2. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL2 in combination with pembrolizumab at PDL1 according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study. |
| Escalation: DL 3 Quavonlimab + Pembro: Cohort 3 | Experimental | Biological: Quavonlimab, Biological: PembrolizumabOn Cycle 1, Day 1 of the Dose Escalation Phase, participants with advanced solid tumors except NSCLC receive a single monotherapy dose lead-in with quavonlimab at DL3. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL3 in combination with pembrolizumab at PDL1 according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study. |
| Confirmation: DL 1 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm A | Experimental | Biological: Quavonlimab, Biological: PembrolizumabOn Cycle 1, Day 1 of the Dose Confirmation Phase and during all subsequent cycles, participants with NSCLC receive quavonlimab at DL1 in combination with pembrolizumab at PDL1, both according to Schedule 1. Participants will be treated for up to 35 cycles total on study. |
| Confirmation: DL 1 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm B | Experimental | Biological: Quavonlimab, Biological: PembrolizumabOn Cycle 1, Day 1 of the Dose Confirmation Phase, participants with NSCLC receive quavonlimab at DL1 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and quavonlimab at DL1 according to Schedule 2. Participants will be treated for up to 35 cycles total on study. |
| Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm C | Experimental | Biological: Quavonlimab, Biological: PembrolizumabOn Cycle 1, Day 1 of the Dose Confirmation Phase, participants with NSCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and at DL2 quavonlimab according to Schedule 2. Participants will be treated for up to 35 cycles total on study. |
| Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (SCLC): Arm D | Experimental | Biological: Quavonlimab, Biological: PembrolizumabOn Cycle 1, Day 1 of the Dose Confirmation Phase, participants with SCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and quavonlimab at DL2 according to Schedule 2. Participants will be treated for up to 35 cycles total on study. |
| Confirmation: DL 2 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm E | Experimental | Biological: Quavonlimab, Biological: PembrolizumabOn Cycle 1, Day 1 of the Dose Confirmation Phase and during all subsequent cycles, participants with NSCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1 according to Schedule 1. Participants will be treated for up to 35 cycles total on study. |
| Expansion: DL1 Quavonlimab Schedule 2+PDL2 Pembro Schedule 2: Arm F | Experimental | Biological: Quavonlimab, Biological: PembrolizumabOn Cycle 1, Day 1 of the Efficacy Expansion Phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma receive quavonlimab at DL1 in combination with pembrolizumab at pembrolizumab dose level 2 (PDL2). Both quavonlimab and pembrolizumab will be administered according to Schedule 2 for up to 24 months on study. |
| Expansion: DL1 Quavonlimab Schedule 2 Monotherapy: Arm G | Experimental | Biological: QuavonlimabOn Cycle 1, Day 1 of the Efficacy Expansion Phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma receive quavonlimab at DL1 according to Schedule 2 for up to 24 months on study. Participants who demonstrate radiographically confirmed progressive disease in Arm G will be eligible to receive combination therapy with pembrolizumab (crossover). |
| Coformulation: Pembrolizumab/Quavonlimab Schedule 2: Arm I | Experimental | Drug: Pembrolizumab/QuavonlimabOn Cycle 1, Day 1 of the Coformulation Phase and during all subsequent cycles, participants with advanced/metastatic solid tumors receive pembrolizumab/quavonlimab according to Schedule 2 for up to 24 months on study. |
| Coformulation Phase in China: Pembrolizumab/Quavonlimab Schedule 2: Arm K | Experimental | Drug: Pembrolizumab/QuavonlimabOn Cycle 1, Day 1 of the Coformulation Phase and during all subsequent cycles, participants in mainland China with advanced solid tumors receive pembrolizumab/quavonlimab according to Schedule 2 for up to 24 months on study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor (except NSCLC for Cohorts 2 and 3) by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit
- Have newly diagnosed histologically or cytologically-confirmed stage IIIB/stage IV NSCLC. Epidermal growth factor receptor (EGFR)-and anaplastic lymphoma kinase (ALK) translocation-directed therapy is not indicated as primary therapy. Participant must not have received prior systemic treatment for advanced NSCLC or must have received previous neoadjuvant and adjuvant chemotherapies ≥6 months before dosing of study drug if prior systemic treatment was given for early stage disease
- Have histologically- or cytologically-confirmed metastatic (Stage III/IV) SCLC with progressive disease after ≥1 platinum-based chemotherapy regimen. Participants with platinum-sensitive disease are eligible
- Have measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology
- Have Eastern Cooperative Oncology Group (ECOG) Performance Scale status of 0 or 1
Key exclusion criteria (27 listed)
- For all phases of the study: Has received previous treatment with another agent targeting cytotoxic T lymphocyte leukocyte antigen (CTLA)-4
- Has received previous treatment with another agent targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
- Has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment
- Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of quavonlimab.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QuavonlimabAlso: MK-1308Quavonlimab is administered intravenously (IV) during the Dose Escalation Phase and Dose Confirmation Phase at either DL1 or DL2, and is administered IV during the Efficacy Expansion Phase at DL2. | Biological | Confirmation: DL 1 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm A, Confirmation: DL 1 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm B, Confirmation: DL 2 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm E, Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm C, Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (SCLC): Arm D, Escalation: DL 2 Quavonlimab + Pembro: Cohort 2, Escalation: DL 3 Quavonlimab + Pembro: Cohort 3, Escalation: Dose Level (DL) 1 Quavonlimab + Pembro: Cohort 1, Expansion: DL1 Quavonlimab Schedule 2 Monotherapy: Arm G, Expansion: DL1 Quavonlimab Schedule 2+PDL2 Pembro Schedule 2: Arm F |
| PembrolizumabAlso: Keytruda®Pembrolizumab is administered IV at PDL1 on Day 1 of each cycle starting Cycle 2 for the Dose Escalation Phase or starting Cycle 1 of the Dose Confirmation Phase. Pembrolizumab is administered IV at PDL2 on Day 1 of each cycle for the Efficacy Expansion Phase (Arm G). | Biological | Confirmation: DL 1 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm A, Confirmation: DL 1 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm B, Confirmation: DL 2 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm E, Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm C, Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (SCLC): Arm D, Escalation: DL 2 Quavonlimab + Pembro: Cohort 2, Escalation: DL 3 Quavonlimab + Pembro: Cohort 3, Escalation: Dose Level (DL) 1 Quavonlimab + Pembro: Cohort 1, Expansion: DL1 Quavonlimab Schedule 2+PDL2 Pembro Schedule 2: Arm F |
| Pembrolizumab/QuavonlimabAlso: MK-1308APembrolizumab/Quavonlimab is a coformulated product composed of quavonlimab at DL1 in combination with pembrolizumab at dose level 2 (PDL2). | Drug | Coformulation Phase in China: Pembrolizumab/Quavonlimab Schedule 2: Arm K, Coformulation: Pembrolizumab/Quavonlimab Schedule 2: Arm I |
Primary outcome
Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT)
Time frame: Up to 6 weeks
DLT was defined as toxicity that is possibly, probably, or definitely related to study therapy and may result in a change in the given dose. DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days (except thrombocytopenia); most non-hematologic AEs ≥ Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for >1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 or 3 of Dose Escalation or Cycle 2 of Dose Confirmation due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity.
Number of Participants With ≥1 Adverse Event (AE)
Time frame: Up to approximately 77 months
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who experienced an AE are presented.
Number of Participants Discontinuing Study Treatment Due to an AE
Time frame: Up to approximately 26 months
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who discontinued study treatment due to an AE are presented.
Efficacy Expansion: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) Based on Adjusted Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time frame: Up to approximately 72 months
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per adjusted Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR in the concurrent randomized subset as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, only data for arms F and G were presented for this endpoint.
10 secondary outcomes
Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab
Time frame: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Maximum Concentration (Cmax) of Pembrolizumab
Time frame: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Minimum Concentration (Cmin) of Pembrolizumab
Time frame: At designated time points up to - Cohorts 1-3: Day 1 Cycle 4, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308)
Time frame: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Maximum Concentration (Cmax) of Quavonlimab
Time frame: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Minimum Concentration (Cmin) of Quavonlimab
Time frame: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs)
Time frame: Cohorts 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycles 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days.
Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs)
Time frame: Cohort 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycle 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, G, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days.
Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1
Time frame: Up to approximately 72 months
Efficacy Expansion: Duration of Response (DOR) as Assessed by BICR Based on Adjusted RECIST v1.1
Time frame: Up to approximately 72 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33276076Perets R, Bar J, Rasco DW, Ahn MJ, Yoh K, Kim DW, Nagrial A, Satouchi M, Lee DH, Spigel DR, Kotasek D, Gutierrez M, Niu J, Siddiqi S, Li X, Cyrus J, Chackerian A, Chain A, Altura RA, Cho BC. Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer. Ann Oncol. 2021 Mar;32(3):395-403. doi: 10.1016/j.annonc.2020.11.020. Epub 2020 Dec 2.
- Results publication: PubMed 34371366Cho BC, Yoh K, Perets R, Nagrial A, Spigel DR, Gutierrez M, Kim DW, Kotasek D, Rasco D, Niu J, Satouchi M, Ahn MJ, Lee DH, Maurice-Dror C, Siddiqi S, Ren Y, Altura RA, Bar J. Anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer. Lung Cancer. 2021 Sep;159:162-170. doi: 10.1016/j.lungcan.2021.07.009. Epub 2021 Jul 18.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
53 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Quavonlimab, Pembrolizumab and Pembrolizumab/Quavonlimab in people with Advanced Solid Tumors, run by Merck Sharp & Dohme LLC at 53 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in Australia, United States, Canada, France, Spain and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT) (time frame: Up to 6 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03179436, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2025.