MelanomaPhase 2PLATforMNCT03484923
Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
A Phase 2 study testing PDR001, LAG525 and INC280 in people with Melanoma, run by Novartis Pharmaceuticals at 30 sites in 10 countries.
Trial summary
The primary purpose of this study is to evaluate the efficacy of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- PDR001, LAG525 and INC280
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 196 participants
- Where
- 30 sitesin 10 countries
- Study dates
- 10 Sep 2018to 30 Dec 2022
- Phase
- Phase 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
- Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma using AJCC edition 8.
- Previously treated for unresectable or metastatic melanoma:
- Subjects with V600BRAF wild-type disease had to have received prior systemic therapy for unresectable or metastatic melanoma with anti-PD-1/PD-L1. Additionally, subjects may have received anti-CTLA-4 as a single agent or in combination with anti-PD-1/PD-L1, irrespective of the sequence. No additional systemic treatment was allowed for advanced or metastatic melanoma.
- A maximum of two prior lines of systemic therapies for unresectable or metastatic melanoma were allowed.
- The last dose of prior therapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4) had to have been received more than four weeks before randomization.
- Subjects with V600BRAF mutant disease had to have received prior systemic therapy for unresectable or metastatic melanoma with anti-PD-1/PD-L1 and V600BRAF inhibitor. Additionally, subjects may have received anti-CTLA-4 as a single agent or in combination with anti-PD-1/PD-L1, or MEK inhibitor (in combination with V600BRAF inhibitor or as a single agent), irrespective of the sequence. No additional systemic treatment was allowed for advanced or metastatic melanoma.
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- A maximum of three prior lines of systemic therapies for unresectable or metastatic melanoma were allowed.
- The last dose of prior therapy had to have been received more than 4 weeks (for anti-PD-1, anti-PD-L1, or anti-CTLA-4) or more than 2 weeks (for V600BRAF or MEK inhibitor) prior to randomization.
- All subjects (with V600BRAF wild-type disease and with V600BRAF mutant disease) had to have documented disease progression as per RECIST v1.1 while on/after the last therapy received prior to study entry and while on/after treatment with anti-PD1/PD-L1. The last progression had to have occurred within 12 weeks prior to randomization in the study.
- ECOG performance status 0-2.
- At least one measurable lesion per RECIST v1.1.
- At least one lesion, suitable for sequential mandatory tumor biopsies (screening and on-treatment) in accordance with the biopsy guidelines specified in the protocol. The same lesion had to be biopsied sequentially.
- Screening tumor biopsy had to fulfill the tissue quality criteria outlined in the protocol, as assessed by a local pathologist.
- Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma according to AJCC Edition 8.
- Previously treated for unresectable or metastatic melanoma:
- All subjects had to have received anti-PD-1 checkpoint inhibitor therapy (i.e., pembrolizumab or nivolumab) either as monotherapy or in combination with ipilimumab as the last systemic therapy prior to enrollment and had to have confirmed disease progression as per RECIST v1.1 (confirmed on a subsequent scan, which could be the scan performed during screening) while on or after this therapy prior to enrollment.
- Subjects with V600BRAF wild-type disease had to have received no more than 2 prior systemic therapies, including prior anti-PD-1/PD-L1 (as monotherapy or in combination with ipilimumab).
- Subjects with V600BRAF mutant disease had to have received no more than 3 prior systemic therapies, including anti-PD-1/PD-L1 (as monotherapy or in combination with ipilimumab) and V600BRAF inhibitor (as monotherapy or in combination with a MEK inhibitor).
- The last dose of anti-PD-1-based therapy had to have been received more than four weeks prior to the first dose of study treatment.
- The last documented disease progression had to have occurred within 12 weeks prior to the first dose of study treatment.
- No additional systemic treatment was allowed for advanced or metastatic melanoma (this included, for example, tumor-infiltrating lymphocyte therapy).
- ECOG performance status 0-1.
- At least one measurable lesion per RECIST v1.1.
- Subjects had to have a baseline tumor sample that was positive for LAG-3 per central assessment.
Who cannot join
- Subjects with uveal or mucosal melanoma.
- Presence of clinically active or unstable brain metastasis at the time of screening.
- Use of any live vaccines against infectious diseases within 3 months before randomization/enrollment.
- Active infection requiring systemic antibiotic therapy at the time of randomization/enrollment.
- Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization/enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone equivalent, were permitted in the absence of active autoimmune disease.
- Active, known or suspected autoimmune disease or a documented history of autoimmune disease.
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- Prior allogenic bone marrow or solid organ transplant.
- History of known hypersensitivity to any of the investigational drugs used in this study.
- Malignant disease, other than that being treated in this study.
- Prior systemic therapy for unresectable or metastatic melanoma with any investigational agent or with any other agent except anti-PD-1/PD-L1 and anti-CTLA-4 (and V600BRAF and MEK inhibitors if the subject has V600BRAF mutant disease). Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months before the start of the study treatment.
- Medical history or current diagnosis of myocarditis.
- Cardiac Troponin T (or Troponin I) level > 2 x ULN at screening.
Trial locations and contacts
30 sites in 10 countries.
30 sites in 10 countries
United States6 sites
Massachusetts General Hospital Massachusetts Gen. Hospital CC
Boston, Massachusetts, 02114
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
University of California Los Angeles
Los Angeles, California, 90095
NYU Laura and Isaac Perlmutter Cancer Center Perlmutter Cancer Center
New York, New York, 10016
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
UCSF Medical Center .
San Francisco, California, 94143
Germany5 sites
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
München, 81377
France3 sites
Novartis Investigative Site
Marseille, 13009
Novartis Investigative Site
Paris, 75475
Novartis Investigative Site
Villejuif, 94800
Italy3 sites
Novartis Investigative Site
Bergamo, BG, 24127
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Naples, 80131
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Madrid, 28009
United Kingdom3 sites
Novartis Investigative Site
London, SW3 6JJ
Novartis Investigative Site
Manchester, M20 4BX
Novartis Investigative Site
Northwood, Middlesex, HA6 2RN
Australia2 sites
Novartis Investigative Site
North Sydney, New South Wales, 2060
Novartis Investigative Site
Westmead, New South Wales, 2145
Canada2 sites
Novartis Investigative Site
Montreal, Quebec, H3T 1E2
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Netherlands2 sites
Novartis Investigative Site
Amsterdam, 1066 CX
Novartis Investigative Site
Rotterdam, 3015 GD
About this study
Official title: A Randomized, Open-label, Phase II Open Platform Study Evaluating the Efficacy and Safety of Novel Spartalizumab (PDR001) Combinations in Previously Treated Unresectable or Metastatic Melanoma
The primary purpose of this study is to evaluate the efficacy of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma
Read the detailed description
This study was a randomized, open-label, two-part, multi-center, open platform phase II study designed to evaluate the efficacy and safety of the anti-PD-1 antibody PDR001 in combination with novel agents for previously treated unresectable or metastatic melanoma. Additionally, a non-randomized single-arm was added based on interim analysis findings to assess the efficacy and safety of PDR001 in combination with LAG525 in subjects with previously treated unresectable or metastatic LAG-3 positive melanoma.
The study consisted of two parts: the selection part and the expansion part, which were applicable to both the randomized and non-randomized sections. In the randomized section, participants were randomized to one of four combination arms available for enrollment:
- Arm 1: LAG525 600 mg intravenously (i.v.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.
- Arm 2: INC280 400 mg orally (p.o.) twice daily (BID) and PDR001 400 mg i.v. Q4W.
- Arm 3: ACZ885 300 mg subcutaneously (s.c.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.
- Arm 4: LEE011 600 mg p.o. once daily (QD) on Days 1-21 of a 28-day cycle and PDR001 400 mg i.v. Q4W.
At each interim analysis, the following determinations were made: (1) which arm met the pre-specified efficacy criteria and expanded to the expansion part, (2) which arms continued enrollment in selection part (up to 45 subjects), and (3) which arms were discontinued due to futility, considering efficacy, safety, and biomarker data. The expansion phase included enrollment of subjects only in the combination arms that met the pre-specified criteria in selection part.
In the non-randomized section, a single combination arm was opened for enrollment in selection part:
- Arm 1A: LAG525 600 mg i.v. Q4W and PDR001 400 mg i.v. Q4W, assessed in a population selected based on the LAG-3 status of their tumor.
Arm 1A would be eligible for enrollment in expansion part only if it met the pre-specified criterion for this arm.
Participants received the study treatment corresponding to their assigned arm on a 28-day cycle basis until disease progression, as determined by local assessment using RECIST v1.1 criteria, or until certain events occurred, such as unacceptable toxicity, initiation of subsequent anti-cancer therapy, withdrawal of consent, investigator's decision, loss to follow-up, death, or termination of the study by the sponsor. Following discontinuation of the study treatment, all subjects were monitored for safety evaluations for up to 150 days after their last dose of the study treatment.
- Conditions
- Melanoma
- Being tested
- PDR001, LAG525, INC280, ACZ885, LEE011
- Keywords
- Unresectable, melanoma, metastatic melanoma, advanced melanoma, spartalizumab, PDR001, LAG525, capmatinib, INC280, canakinumab, ACZ885, ribociclib, LEE011, immunotherapy, platform study, LAG-3
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDR001Drug
Also called Spartalizumab
400 mg of PDR001 administered every 4 weeks intravenously
LAG525Drug
Also called Ieramilimab
600 mg of LAG525 administered every 4 weeks intravenously
INC280Drug
Also called Capmatinib
400 mg of INC280 administered twice daily orally
ACZ885Drug
Also called Canakinumab
200 mg of ACZ885 administered every 4 weeks subcutaneosuly
LEE011Drug
Also called Ribociclib
600 mg of LEE011 orally taken once daily on Days 1-21 of a 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: LAG525 + PDR001 (randomized section) | Experimental | Participnats randomized to receive LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks Receives: Drug: PDR001; Drug: LAG525 |
| Arm 2: INC280+PDR001 (randomized section) | Experimental | Participants randomized to receive INC280 orally at a dosage of 400 mg twice daily, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks Receives: Drug: PDR001; Drug: INC280 |
| Arm 3: ACZ885 + PDR001 (randomized section) | Experimental | Participants randomized to receive to receive ACZ885 at a dosage of 300 mg administered subcutaneously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks Receives: Drug: PDR001; Drug: ACZ885 |
| Arm 4: LEE011 + PDR001 (randomized section) | Experimental | Participants randomized to receive LEE011 orally at a dosage of 600 mg once daily on Days 1-21 of a 28-day cycle, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks Receives: Drug: PDR001; Drug: LEE011 |
| Arm 1A: LAG525 + PDR001 (non-randomized section) | Experimental | LAG-3 positive participants received LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks Receives: Drug: PDR001; Drug: LAG525 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
ORR defined as the percentage of patients with a best overall response of either confirmed complete response (CR) or partial response (PR) as per local review by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and assessed by computed tomography (CT)/ magnetic resonance imaging (MRI).
CR:Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: Up to 49 months (randomized section) and 18 months (non-randomized section)
Secondary outcomes (11)
Duration of Response (DOR)
DOR defined as the time from date of first documented CR or PR to date of first documented disease progression (as per local review by RECIST v1.1 and assessed by CT/MRI) or death due to any cause. Subjects continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment.
CR:Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: From first documented response to disease progression or death due to any cause, whichever occurs first, assessed up to 49 months (randomized part) and 18 months (non-randomized part)
Overall Survival (OS)
OS was defined as the time from date of randomization (or date of first dose of study treatment in non-randomized part) to date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method, and the medians and 95% confidence intervals of the medians were presented.
Measured: From randomization (or start of treatment for non-randomized section) to death due to any cause, assessed up to 49 months (randomized section) and 24 months (non-randomized section)
Progression Free Survival (PFS)
PFS was defined as the time between the date of randomization (or date of first dose of study treatment in non-randomized section) to the date of event defined as the first documented disease progression (as per local review by RECIST v1.1 and assessed by CT/MRI) or death due to any cause. If a subject had not had an event before leaving study or initiation of subsequent anticancer therapy, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using the Kaplan-Meier method, medians and 95% confidence interval of the medians were presented.
Measured: From randomization (or start of treatment for non-randomized section) to disease progression or death due to any cause, whichever occurs first, assessed up to 49 months (randomized section) and 18 months (non-randomized section)
Disease Control Rate (DCR)
DCR was defined as the percentage of participants with best overall response of CR, PR or stable disease (SD) (as per local review by RECIST v1.1 and assessed by CT/MRI).
CR:Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Measured: Up to 49 months (randomized section) and 18 months (non-randomized section)
Percentage of Participants With PDR001 Anti-drug Antibodies (ADA) Positive Result at Baseline
Percentage of participants who had a PDR001 ADA positive result at baseline.
Measured: At Baseline
Percentage of Participants With LAG525 Anti-drug Antibodies (ADA) Positive Result at Baseline
Percentage of participants who had a LAG525 ADA positive result at baseline. Only applicable for participants enrolled in Arm 1 and Arm 1A.
Measured: At Baseline
Percentage of Participants With ACZ885 Anti-drug Antibodies (ADA) Positive Result at Baseline
Percentage of participants who had an ACZ885 ADA positive result at baseline. Only applicable for subjects enrolled in Arm 3.
Measured: At Baseline
Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for PDR001
Percentage of participants who tested positive for treatment-induced ADA for PDR001 (subjects with ADA-negative sample at baseline with at least one post-baseline ADA positive sample) as well as treatment-boosted ADA for PDR001 (subjects with baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment).
Measured: Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT), EOT, and 30 and 150 days post-EOT (assessed up to 49 months randomized section and 24 months non-randomized section). Cycle= 28 days
Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for LAG525
Percentage of participants who tested positive for treatment-induced ADA for LAG525 (subjects with ADA-negative sample at baseline with at least one post-baseline ADA positive sample) as well as treatment-boosted ADA for LAG525 (subjects with baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment). Only applicable for subjects enrolled in Arm 1 and Arm 1A.
Measured: Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT) and EOT (assessed up to 49 months in the randomized section and 18 months in the non-randomized section). Cycle= 28 days
Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for ACZ885
Percentage of participants who tested positive for treatment-induced ADA for ACZ885 (subjects with ADA-negative sample at baseline with at least one post-baseline ADA positive sample) as well as treatment-boosted ADA for ACZ885 (subjects with baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment). Only applicable for subjects enrolled in Arm 3.
Measured: Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT) and EOT (assessed up to 40 months). Cycle= 28 days
Percentage of Participants With a Favorable Biomarker Profile (pFBP)
Biomarker parameters included: 1) number of tumor infiltrating T cells (TIL), 2) activation level of TIL, and 3) changes in immune response gene expression signatures. For the number of TILs, an increase in tumoral CD8+ cell numbers compared to baseline was considered favorable. The activation level of TIL was assessed by the percentage of tumoral CD8+ cells expressing GzmB (a marker for cytotoxic activity) or Ki67 (a marker for cell proliferation), where an increase in either GZMB+/CD8+ or KI67+/CD8+ post-baseline was considered favorable. Changes in immune response gene expression signatures were evaluated by the levels in T-cell inflamed signature (TIS), where an increase from baseline was considered favorable.
To be categorized as having a pFBP, a subject must meet the favorable criteria for at least two of the three biomarker parameters. The percentage of participants with pFBP was assessed.
Measured: Baseline and after 3-4 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2018
- Study start10 Sep 2018
- Primary completion30 Dec 2022
- Study completion30 Dec 2022
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.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03484923
- Sponsor's protocol ID
- CPDR001J2201
- Other IDs
- 2018-000610-38, 2018
- Acronym
- PLATforM
- Status last verified
- Jun 2024
- First submitted
- 26 Mar 2018
- Last updated
- 18 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Phase II Open Platform Study Evaluating the Efficacy and Safety of Novel Spartalizumab (PDR001) Combinations in Previously Treated Unresectable or Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT03484923
- Acronym / sponsor ID
- PLATforM / CPDR001J2201
- Conditions
- Melanoma
- Keywords
- Unresectable, melanoma, metastatic melanoma, advanced melanoma, spartalizumab, PDR001, LAG525, capmatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 196 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 10 Sep 2018 (actual)
- Primary completion
- 30 Dec 2022 (actual)
- Study completion
- 30 Dec 2022 (actual)
- First posted
- 2 Apr 2018 (actual)
- Results
- Posted 18 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to evaluate the efficacy of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma
Detailed description
This study was a randomized, open-label, two-part, multi-center, open platform phase II study designed to evaluate the efficacy and safety of the anti-PD-1 antibody PDR001 in combination with novel agents for previously treated unresectable or metastatic melanoma. Additionally, a non-randomized single-arm was added based on interim analysis findings to assess the efficacy and safety of PDR001 in combination with LAG525 in subjects with previously treated unresectable or metastatic LAG-3 positive melanoma.
The study consisted of two parts: the selection part and the expansion part, which were applicable to both the randomized and non-randomized sections. In the randomized section, participants were randomized to one of four combination arms available for enrollment:
- Arm 1: LAG525 600 mg intravenously (i.v.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.
- Arm 2: INC280 400 mg orally (p.o.) twice daily (BID) and PDR001 400 mg i.v. Q4W.
- Arm 3: ACZ885 300 mg subcutaneously (s.c.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.
- Arm 4: LEE011 600 mg p.o. once daily (QD) on Days 1-21 of a 28-day cycle and PDR001 400 mg i.v. Q4W.
At each interim analysis, the following determinations were made: (1) which arm met the pre-specified efficacy criteria and expanded to the expansion part, (2) which arms continued enrollment in selection part (up to 45 subjects), and (3) which arms were discontinued due to futility, considering efficacy, safety, and biomarker data. The expansion phase included enrollment of subjects only in the combination arms that met the pre-specified criteria in selection part.
In the non-randomized section, a single combination arm was opened for enrollment in selection part:
- Arm 1A: LAG525 600 mg i.v. Q4W and PDR001 400 mg i.v. Q4W, assessed in a population selected based on the LAG-3 status of their tumor.
Arm 1A would be eligible for enrollment in expansion part only if it met the pre-specified criterion for this arm.
Participants received the study treatment corresponding to their assigned arm on a 28-day cycle basis until disease progression, as determined by local assessment using RECIST v1.1 criteria, or until certain events occurred, such as unacceptable toxicity, initiation of subsequent anti-cancer therapy, withdrawal of consent, investigator's decision, loss to follow-up, death, or termination of the study by the sponsor. Following discontinuation of the study treatment, all subjects were monitored for safety evaluations for up to 150 days after their last dose of the study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm 1: LAG525 + PDR001 (randomized section) | Experimental | Drug: PDR001, Drug: LAG525Participnats randomized to receive LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks |
| Arm 2: INC280+PDR001 (randomized section) | Experimental | Drug: PDR001, Drug: INC280Participants randomized to receive INC280 orally at a dosage of 400 mg twice daily, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks |
| Arm 3: ACZ885 + PDR001 (randomized section) | Experimental | Drug: PDR001, Drug: ACZ885Participants randomized to receive to receive ACZ885 at a dosage of 300 mg administered subcutaneously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks |
| Arm 4: LEE011 + PDR001 (randomized section) | Experimental | Drug: PDR001, Drug: LEE011Participants randomized to receive LEE011 orally at a dosage of 600 mg once daily on Days 1-21 of a 28-day cycle, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks |
| Arm 1A: LAG525 + PDR001 (non-randomized section) | Experimental | Drug: PDR001, Drug: LAG525LAG-3 positive participants received LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma using AJCC edition 8.
- Previously treated for unresectable or metastatic melanoma:
- A maximum of two prior lines of systemic therapies for unresectable or metastatic melanoma were allowed.
- The last dose of prior therapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4) had to have been received more than four weeks before randomization.
- Subjects with V600BRAF mutant disease had to have received prior systemic therapy for unresectable or metastatic melanoma with anti-PD-1/PD-L1 and V600BRAF inhibitor. Additionally, subjects may have received anti-CTLA-4 as a single agent or in combination with anti-PD-1/PD-L1, or MEK inhibitor (in combination with V600BRAF inhibitor or as a single agent), irrespective of the sequence. No additional systemic treatment was allowed for advanced or metastatic melanoma.
Key exclusion criteria (12 listed)
- Subjects with uveal or mucosal melanoma.
- Presence of clinically active or unstable brain metastasis at the time of screening.
- Use of any live vaccines against infectious diseases within 3 months before randomization/enrollment.
- Active infection requiring systemic antibiotic therapy at the time of randomization/enrollment.
- Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization/enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone equivalent, were permitted in the absence of active autoimmune disease.
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 |
|---|---|---|
| PDR001Also: Spartalizumab400 mg of PDR001 administered every 4 weeks intravenously | Drug | Arm 1: LAG525 + PDR001 (randomized section), Arm 1A: LAG525 + PDR001 (non-randomized section), Arm 2: INC280+PDR001 (randomized section), Arm 3: ACZ885 + PDR001 (randomized section), Arm 4: LEE011 + PDR001 (randomized section) |
| LAG525Also: Ieramilimab600 mg of LAG525 administered every 4 weeks intravenously | Drug | Arm 1: LAG525 + PDR001 (randomized section), Arm 1A: LAG525 + PDR001 (non-randomized section) |
| INC280Also: Capmatinib400 mg of INC280 administered twice daily orally | Drug | Arm 2: INC280+PDR001 (randomized section) |
| ACZ885Also: Canakinumab200 mg of ACZ885 administered every 4 weeks subcutaneosuly | Drug | Arm 3: ACZ885 + PDR001 (randomized section) |
| LEE011Also: Ribociclib600 mg of LEE011 orally taken once daily on Days 1-21 of a 28-day cycle | Drug | Arm 4: LEE011 + PDR001 (randomized section) |
Primary outcome
Overall Response Rate (ORR)
Time frame: Up to 49 months (randomized section) and 18 months (non-randomized section)
ORR defined as the percentage of patients with a best overall response of either confirmed complete response (CR) or partial response (PR) as per local review by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and assessed by computed tomography (CT)/ magnetic resonance imaging (MRI). CR:Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
11 secondary outcomes
Duration of Response (DOR)
Time frame: From first documented response to disease progression or death due to any cause, whichever occurs first, assessed up to 49 months (randomized part) and 18 months (non-randomized part)
Overall Survival (OS)
Time frame: From randomization (or start of treatment for non-randomized section) to death due to any cause, assessed up to 49 months (randomized section) and 24 months (non-randomized section)
Progression Free Survival (PFS)
Time frame: From randomization (or start of treatment for non-randomized section) to disease progression or death due to any cause, whichever occurs first, assessed up to 49 months (randomized section) and 18 months (non-randomized section)
Disease Control Rate (DCR)
Time frame: Up to 49 months (randomized section) and 18 months (non-randomized section)
Percentage of Participants With PDR001 Anti-drug Antibodies (ADA) Positive Result at Baseline
Time frame: At Baseline
Percentage of Participants With LAG525 Anti-drug Antibodies (ADA) Positive Result at Baseline
Time frame: At Baseline
Percentage of Participants With ACZ885 Anti-drug Antibodies (ADA) Positive Result at Baseline
Time frame: At Baseline
Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for PDR001
Time frame: Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT), EOT, and 30 and 150 days post-EOT (assessed up to 49 months randomized section and 24 months non-randomized section). Cycle= 28 days
Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for LAG525
Time frame: Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT) and EOT (assessed up to 49 months in the randomized section and 18 months in the non-randomized section). Cycle= 28 days
Percentage of Participants Who Were Treatment-induced ADA Positive and Treatment-boosted ADA Positive for ACZ885
Time frame: Pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 5, 6 and thereafter every 3 cycles until end of treatment (EOT) and EOT (assessed up to 40 months). Cycle= 28 days
Percentage of Participants With a Favorable Biomarker Profile (pFBP)
Time frame: Baseline and after 3-4 weeks of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Patient Lay Trial SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
30 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PDR001, LAG525 and INC280 in people with Melanoma, run by Novartis Pharmaceuticals at 30 sites in 10 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 24 inclusion and 12 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 18 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Germany, France, Italy, Spain and 5 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 phase mean?
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 18 Jan 2024). 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?
Overall Response Rate (ORR) (time frame: Up to 49 months (randomized section) and 18 months (non-randomized section)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jun 2024.