Squamous Cell Carcinoma of Head and NeckPhase 1/2NCT03829501
A Phase 1/2, Open-label, Multi-center Study of the Safety and Efficacy of Alomfilimab (KY1044) as Single Agent and in Combination With Anti-PD-L1 (Atezolizumab) in Adult Patients With Selected Advanced Malignancies
A Phase 1/2 study testing Alomfilimab and Atezolizumab in people with Squamous Cell Carcinoma of Head and Neck and Non-small Cell Lung Cancer, run by Kymab Limited at 22 sites in 6 countries.
Trial summary
A Phase 1/2, open label, multi-center study to evaluate the safety, efficacy and tolerability of alomfilimab as single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients with selected advanced malignancies, who are ineligible for or there are no available therapies known to confer a clinical… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of Head and Neck, Non-small Cell Lung Cancer, Hepatocellular Carcinoma
- What is being tested?
- Alomfilimab and Atezolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 222 participants
- Where
- 22 sitesin 6 countries
- Study dates
- 28 Jan 2019to 3 Oct 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
- Age ≥18 years (≥20 years in Taiwan)
- Histologically documented advanced/metastatic malignancies
- Phase 1 and Phase 2 participants with advanced/metastatic malignancies who have measurable disease (non-measurable disease is allowed only in Phase 1) as determined by RECIST 1.1 will be eligible if, according to the National Comprehensive Cancer Network (NCCN) guidelines, there are no available therapies known to confer a clinical benefit for their disease, or they have exhausted all such available options. Additionally, the following specific tumor indications will be enrolled:
- Phase 1: Participants with advanced/metastatic malignancies, and preferred indications (non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), melanoma, cervical, esophageal, gastric, renal, pancreatic, and triple negative breast cancer)
- Phase 2 Alomfilimab single agent: Participants with advanced/metastatic malignancies in indications in which signs of anti-tumor activity (Complete Response (CR), Partial Response (PR) or durable stable disease (SD) with tumor shrinkage that does not qualify for PR) were seen during the dose escalation of Alomfilimab as single agent
- Phase 2 Alomfilimab in combination with atezolizumab: Participants with advanced/metastatic malignancies in the selected indications below, and/or indications which have shown promising activity in Phase 1:
Show all 16Show fewer
- NSCLC (anti-PD-(L)1 therapy naïve and pre-treated between 1 and 2 prior lines of systemic therapy for advanced disease)
- Gastric (anti-PD-(L)1 therapy naïve and pre-treated)
- Recurrent and/or metastatic HNSCC (anti-PD-(L)1 therapy naïve and pre-treated between 1 and 2 prior lines of systemic therapy for advanced disease)
- Esophageal (anti-PD-(L)1 therapy naïve and pre-treated)
- Cervical (anti-PD-(L)1 therapy naïve and pre-treated)
- Indications, in which signs of anti-tumor activity has been observed in Phase 1 with Alomfilimab in combination with atezolizumab
- Prior therapy with anti-PD-(L)1 inhibitors is allowed provided any toxicity attributed to prior anti-PD-(L)1-directed therapy did not lead to discontinuation of therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Life expectancy longer than 12 weeks
- Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Participants must be willing to undergo a new tumor biopsy at screening, and during therapy on the study
Who cannot join
- Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior 2 weeks of first dose of study treatment
- History of severe hypersensitivity reactions to other monoclonal antibodies and/or their excipients
- Known presence of neutralizing anti-atezolizumab antibodies (for patients previously treated with atezolizumab)
- Having out of range laboratory values: creatinine, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), absolute neutrophil count (ANC), platelet count, hemoglobin
- Impaired cardiac function or clinically significant cardiac disease, including any of the following:
- Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association [NYHA] Grade ≥2), uncontrolled hypertension or clinically significant arrhythmia
Show all 21Show fewer
- QTcF >470 msec on screening (electrocardiogram) ECG using Fridericia's formula (QTcF) or congenital long QT syndrome
- Acute myocardial infarction or unstable angina pectoris
- Known human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection
- Malignant disease, other than that being treated in this study
- Any medical condition that would, in the Investigator's judgment, prevent participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results
- Active autoimmune disease or a documented history of autoimmune disease
- Participants previously exposed to anti-PD-(L)1 treatment who are not adequately treated for skin rash or had no replacement therapy for endocrinopathies should be excluded
- Participants with a history of drug-induced pneumonitis or current pneumonitis
- Systemic steroid therapy or any immunosuppressive therapy. Topical, inhaled, nasal, and ophthalmic steroids are not prohibited
- Use of live attenuated vaccines against infectious diseases within 4 weeks of the first dose of study treatment. SARS-CoV-2 vaccines authorized for use by the competent local regulatory health authorities for active immunization to prevent COVID 19 are allowed (unless the vaccine is live or live attenuated) and must be given in accordance with the prevailing immunization guidelines.
- Anti-CTLA4, anti-PD-(L)1 treatment within 4 weeks of the first dose of study treatment
- Pre-treatment with anti-CTLA4 antibodies in combination with any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathway
- Presence of Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) ≥Grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if CTCAE v5 ≥Grade 3) due to prior cancer therapy
- Radiotherapy within 2 weeks of the first dose of study treatment, except for palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass. To allow evaluation for response to treatment, participants enrolled in the Phase 2 part must have remaining measurable disease that has not been irradiated
- Pregnant or lactating women
Trial locations and contacts
22 sites in 6 countries.
22 sites in 6 countries
Italy7 sites
Kymab investigational site 3906
Candiolo, Torino, 10060
Kymab investigational site 3904
Meldola, Forlì-Cesena, 47014
Kymab investigational site 3901
Milan
Kymab investigational site 3903
Milan
Kymab investigational site 3902
Naples
Kymab investigational site 3910
Roma
Kymab investigational site 3908
Turin, 10128
United States6 sites
Kymab investigational site 1109
Duarte, California, 91010
Kymab investigator site 1101
Houston, Texas, 77030
Kymab investigational site 1103
Nashville, Tennessee, 37203
Kymab investigational site 1102
New Haven, Connecticut, 06510
Kymab investigational site 1108
Orlando, Florida, 32806
Kymab investigational site 1104
Sarasota, Florida, 34232
United Kingdom4 sites
Kymab investigational site 4405
London
Kymab investigational site 4402
Manchester
Kymab investigational site 4404
Oxford
Kymab investigational site 4401
Sutton
Hungary2 sites
Kymab investigational site 3602
Budapest, 1122
Kymab investigational site 3601
Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400
Taiwan2 sites
Kymab investigational site 8806
Changhua, Changhwa, 505
Kymab investigational site 8801
Taipei
Poland1 site
Kymab investigational site 4801
Siedlce, Masovian Voivodeship, 04-141
About this study
Official title: A Phase 1/2, Open-label, Multi-center Study of the Safety and Efficacy of KY1044 as Single Agent and in Combination With Anti-PD-L1 (Atezolizumab) in Adult Patients With Selected Advanced Malignancies
A Phase 1/2, open label, multi-center study to evaluate the safety, efficacy and tolerability of alomfilimab as single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients with selected advanced malignancies, who are ineligible for or there are no available therapies known to confer a clinical benefit for their disease, or they have exhausted all such available options in each indication and therefore will be patients for whom a clinical trial is appropriate.
- Conditions
- Squamous Cell Carcinoma of Head and Neck, Non-small Cell Lung Cancer, Hepatocellular Carcinoma, Esophageal Cancer, Gastric Cancer, Melanoma
- Being tested
- Alomfilimab, Atezolizumab
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Carcinoma, Hepatocellular, Esophageal Neoplasms, Stomach Neoplasms, Melanoma, Carcinoma, Renal Cell, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlomfilimabDrug
Also called KY1044, SAR445256
A human anti-ICOS monoclonal antibody
AtezolizumabDrug
Also called TECENTRIQ
An anti-PD-L1 monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Alomfilimab Monotherapy | Experimental | Participants will receive alomfilimab 0.8 to 240 mg as a single agent via intravenous (IV) infusion every 3 weeks (Q3W). Receives: Drug: Alomfilimab |
| Phase 1: Alomfilimab + Atezolizumab Combination Therapy | Experimental | Participants will receive alomfilimab 2.4 to 80 mg in combination with atezolizumab 1200 mg via IV infusion Q3W. Receives: Drug: Alomfilimab; Drug: Atezolizumab |
| Phase 2: Alomfilimab + Atezolizumab in Anti-PD-(L)1 Naïve Participants | Experimental | Anti-PD-(L)1 naïve participants with pancreatic cancer, triple negative breast cancer (BC) or head and neck squamous cell carcinoma (HNSCC) will receive alomfilimab 2.4 to 24 mg in combination with atezolizumab 1200 mg via IV infusion Q3W. Receives: Drug: Alomfilimab; Drug: Atezolizumab |
| Phase 2: Alomfilimab + Atezolizumab in Pre-treated Participants | Experimental | Pre-treated participants with pancreatic cancer, triple negative BC or HNSCC will receive alomfilimab 2.4 to 24 mg in combination with atezolizumab 1200 mg via IV infusion Q3W. Receives: Drug: Alomfilimab; Drug: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. An serious AE (SAE) was any AE that:
- resulted in death;
- was life-threatening;
- resulted in inpatient hospitalization or prolongation of existing hospitalization;
- resulted in a persistent or significant disability/incapacity;
- resulted in congenital anomaly/birth defect in the offspring of a participant who received IMPs;
- constituted an important medical event.
Clinically significant changes in laboratory parameters, vital signs and electrocardiogram results were reported as AEs. A TEAE was defined as an AE observed after starting administration of the specific treatment.
Measured: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks
Phase 1: Number of Participants Experiencing Dose Changes
Dose changes were defined as infusion interruption and dose reduction.
Measured: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks
Phase 1: Absolute Dose Intensity
Absolute dose intensity was calculated as cumulative dose received (mg) / study treatment duration (weeks).
Measured: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks
Phase 1: Relative Dose Intensity
Relative dose intensity was calculated as the cumulative dose received (mg) / initial planned cumulative dose (mg). Initial planned cumulative dose was calculated as the starting dose multiplied by the scheduled number of administrations within the study treatment duration.
Measured: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks
Phase 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
A DLT was defined as a clinically relevant AE or abnormal laboratory value of Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) ≥ Grade 3 assessed as unrelated to disease, PD, inter-current illness or concomitant medications, which occurs within the first cycle (21 days) of treatment with alomfilimab as single agent or in combination with atezolizumab during the dose escalation part of the study.
Measured: From first dose of study treatment (Day 1) up to 21 days
Phase 2: Overall Response Rate (ORR) Per RECIST 1.1
ORR was the percentage of participants with a measurable disease at baseline and with a confirmed response of complete response (CR) or partial response (PR) according to RECIST v1.1 as the best response. The response is confirmed by a later scan conducted at least 4 weeks after the initial response is observed. The 95% confidence interval (CI) was calculated using the exact binomial method (Clopper-Pearson).
CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm. All lymph nodes must have been non-pathological in size (< 10mm short axis).
PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
Measured: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 162 weeks
Secondary outcomes (15)
Best Overall Response (BOR) Per RECIST 1.1
BOR for each participant was defined as the best confirmed response per RECIST 1.1 among all responses recorded from start of treatment until PD, initiation of new anti-cancer therapy, death, or analysis cut-off date, whichever comes first, with responses of:
CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm. All lymph nodes must have been non-pathological in size (< 10mm short axis).
PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.
Not evaluable (NE).
Measured: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively
Progression-free Survival (PFS) Per RECIST 1.1
PFS was calculated as (first documented PD or death due to any cause - first dose date of study drug +1)/30.4375. Participants who were not observed to have progressed or died were censored at the date of the last tumor assessment. Participants who missed two or more sequential assessments were censored at the date of the last tumor assessment before the missed assessments. Participants who started new anti-cancer therapy prior to documented PD were censored at the date of the last tumor assessment prior to the start of the new therapy. Participants who did not have any tumor assessments were censored with a duration of 1 day. PFS was obtained via Kaplan Meier estimation using the Brookmeyer-Crowley method.
PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.
Measured: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively
Duration of Response Per RECIST 1.1
Duration of response was calculated as (date of the first documentation of PD or to death due to any cause in the absence of PD - date of the first documentation of unconfirmed objective response [CR or PR] + 1]/30.4375. Participants who were not observed to have progressed or died were censored at the date of the last tumor assessment. Participants who missed two or more sequential assessments were censored at the date of the last tumor assessment before the missed assessments. Participants who started new anti-cancer therapy prior to documented PD were censored at the date of the last tumor assessment prior to the start of the new therapy. Participants with no disease assessment (or only had assessments with response = NE) after first study treatment or have baseline or post-baseline assessments where the RECIST criteria could not be applied had their duration of response time censored. Duration of response was obtained via Kaplan Meier estimation.
Measured: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively
ORR Per iRECIST
RECIST 1.1 has been modified to take into consideration the unique response kinetics which have been observed with immunotherapy in some patients where responses to immune therapies may occur after progression has been assessed. ORR was the percentage of participants with a measurable disease at baseline and with a confirmed response of complete immune-response (iCR) or partial immune-response (iPR) according to iRECIST as the best response. The 95% CI was calculated using the exact binomial method (Clopper-Pearson).
iCR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm. All lymph nodes must have been non-pathological in size (< 10mm short axis).
iPR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
Measured: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively
PFS Per iRECIST
PFS was calculated as (first documented iPD or death due to any cause - first dose date of study drug +1)/30.4375. Participants who were not observed to have progressed or died were censored at the date of the last tumor assessment. Participants who missed two or more sequential assessments were censored at the date of the last tumor assessment before the missed assessments. Participants who started new anti-cancer therapy prior to documented PD were censored at the date of the last tumor assessment prior to the start of the new therapy. Participants who did not have any tumor assessments were censored with a duration of 1 day. PFS was obtained via Kaplan Meier estimation using the Brookmeyer-Crowley method.
iPD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.
Measured: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively
Phase 1: ORR Per RECIST 1.1
ORR was the percentage of participants with a measurable disease at baseline and with a confirmed response of CR or PR according to RECIST v1.1 as the best response. The response is confirmed by a later scan conducted at least 4 weeks after the initial response is observed. The 95% CI was calculated using the exact binomial method (Clopper-Pearson).
CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm. All lymph nodes must have been non-pathological in size (< 10mm short axis).
PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
Measured: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 weeks
Overall Survival Rate at 12 and 24 Months
Overall Survival rate was defined as the proportion of participants that had known survival status. Overall survival rate was obtained via Kaplan Meier estimation using the complimentary log-log transformation method.
Measured: Months 12 and 24
Phase 2: Number of Participants Experiencing TEAEs
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. An SAE was any AE that:
- resulted in death;
- was life-threatening;
- resulted in inpatient hospitalization or prolongation of existing hospitalization;
- resulted in a persistent or significant disability/incapacity;
- resulted in congenital anomaly/birth defect in the offspring of a participant who received IMPs;
- constituted an important medical event.
Clinically significant changes in laboratory parameters, vital signs and electrocardiogram results were reported as AEs. A TEAE was defined as an AE observed after starting administration of the specific treatment.
Measured: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 86 weeks
Phase 2: Number of Participants Experiencing Dose Changes
Dose changes were defined as infusion interruption and dose reduction.
Measured: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 86 weeks
Phase 2: Absolute Dose Intensity
Absolute dose intensity was calculated as cumulative dose received (mg) / study treatment duration (weeks).
Measured: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 86 weeks
Phase 2: Relative Dose Intensity
Relative dose intensity was calculated as the cumulative dose received (mg) / initial planned cumulative dose (mg). Initial planned cumulative dose was calculated as the starting dose multiplied by the scheduled number of administrations within the study treatment duration.
Measured: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 86 weeks
Phase 1: Maximum Concentration (Cmax) of Alomfilimab
The serum pharmacokinetics (PK) of alomfilimab were characterized using non-compartmental analysis (NCA). Nominal times of sample collections were used for the NCA. All below limit of quantification (BLQ) values were set to 0 units.
Measured: Cycles 1 and 3 Day 1 pre-infusion to 336 hours post-infusion start (21 day cycle length)
Phase 1: Half-life (t1/2) of Alomfilimab
The serum PK of alomfilimab were characterized using NCA. Nominal times of sample collections were used for the NCA. All BLQ values were set to 0 units.
Measured: Cycles 1 and 3 Day 1 pre-infusion to 336 hours post-infusion start (21 day cycle length)
Number of Participants Experiencing Anti-drug Antibodies (ADA) at Anytime
Detection of ADA was assessed from blood samples taken during the study using validated bioanalytical methods. The number of participants who developed detectable anti-alomfilimab or anti-atezolizumab antibodies during any cycle or the safety follow-up period (SFUP) was calculated.
Measured: Phase 1: pre-infusion at all cycles (up to 69 cycles) + 90 days SFUP; Phase 2: pre-infusion at all cycles (up to 28 cycles) + 90 day SFUP (21 day cycle length)
Change From Baseline in Tumor-infiltrating Lymphocytes Per mm^2 at Cycle 2 Day 8
Biological samples (e.g., archived and fresh tumor samples or blood samples) were collected for analysis of responsive biomarkers.
The summary of change in the following markers were calculated:
- FOXP3-ICOS double-positive cells per mm^2 in the Tumor
- CD8-positive cells per mm^2 in the tumor
- CD8-positive cells per mm^2 in the invasive margin.
Measured: Baseline and Cycle 2 Day 8 (21 day cycle length)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2019
- Study start28 Jan 2019
- Primary completion3 Oct 2024
- Study completion3 Oct 2024
Why it stopped: Early discontinuation based on strategic sponsor decision not driven by any safety concerns.
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 (1)Papers the sponsor has linked to this study.
- Other trials for Squamous Cell Carcinoma of Head and NeckStudies of the same condition, open and under way.
- 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 222 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kymab Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03829501
- Sponsor's protocol ID
- KY1044-CT01
- Other IDs
- Sanofi Study ID, 2018-003172-12, U1111-1269-6777, 2018
- Status last verified
- Mar 2025
- First submitted
- 17 Jan 2019
- Last updated
- 2 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at https://vivli.org
Publications
Naing A, Lin CC, Patel MR, Curigliano G, Burris HA, Thistlethwaite F, De Braud F, Minchom A, Ascierto PA, Wake M, Nguyen MA, Abbadessa G, Sainson RCA, Palu CC, Quaratino S, Deantonio C. First-in-human, phase 1, open-label study of alomfilimab, an anti-ICOS antibody, as a single agent and in combination with anti-PD-L1 in advanced malignancies. J Immunother Cancer. 2026 Jun 8;14(6):e013540. doi: 10.1136/jitc-2025-013540.
PubMed 42259602
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open-label, Multi-center Study of the Safety and Efficacy of KY1044 as Single Agent and in Combination With Anti-PD-L1 (Atezolizumab) in Adult Patients With Selected Advanced Malignancies
- ClinicalTrials.gov ID
- NCT03829501
- Acronym / sponsor ID
- KY1044-CT01
- Conditions
- Squamous Cell Carcinoma of Head and Neck, Non-small Cell Lung Cancer, Hepatocellular Carcinoma, Esophageal Cancer, Gastric Cancer, Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early discontinuation based on strategic sponsor decision not driven by any safety concerns.
- Enrolment
- 222 participants (actual)
- Lead sponsor
- Kymab LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Study start
- 28 Jan 2019 (actual)
- Primary completion
- 3 Oct 2024 (actual)
- Study completion
- 3 Oct 2024 (actual)
- First posted
- 4 Feb 2019 (actual)
- Results
- Posted 2 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase 1/2, open label, multi-center study to evaluate the safety, efficacy and tolerability of alomfilimab as single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients with selected advanced malignancies, who are ineligible for or there are no available therapies known to confer a clinical benefit for their disease, or they have exhausted all such available options in each indication and therefore will be patients for whom a clinical trial is appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Alomfilimab Monotherapy | Experimental | Drug: AlomfilimabParticipants will receive alomfilimab 0.8 to 240 mg as a single agent via intravenous (IV) infusion every 3 weeks (Q3W). |
| Phase 1: Alomfilimab + Atezolizumab Combination Therapy | Experimental | Drug: Alomfilimab, Drug: AtezolizumabParticipants will receive alomfilimab 2.4 to 80 mg in combination with atezolizumab 1200 mg via IV infusion Q3W. |
| Phase 2: Alomfilimab + Atezolizumab in Anti-PD-(L)1 Naïve Participants | Experimental | Drug: Alomfilimab, Drug: AtezolizumabAnti-PD-(L)1 naïve participants with pancreatic cancer, triple negative breast cancer (BC) or head and neck squamous cell carcinoma (HNSCC) will receive alomfilimab 2.4 to 24 mg in combination with atezolizumab 1200 mg via IV infusion Q3W. |
| Phase 2: Alomfilimab + Atezolizumab in Pre-treated Participants | Experimental | Drug: Alomfilimab, Drug: AtezolizumabPre-treated participants with pancreatic cancer, triple negative BC or HNSCC will receive alomfilimab 2.4 to 24 mg in combination with atezolizumab 1200 mg via IV infusion Q3W. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age ≥18 years (≥20 years in Taiwan)
- Histologically documented advanced/metastatic malignancies
- Phase 1 and Phase 2 participants with advanced/metastatic malignancies who have measurable disease (non-measurable disease is allowed only in Phase 1) as determined by RECIST 1.1 will be eligible if, according to the National Comprehensive Cancer Network (NCCN) guidelines, there are no available therapies known to confer a clinical benefit for their disease, or they have exhausted all such available options. Additionally, the following specific tumor indications will be enrolled:
- Prior therapy with anti-PD-(L)1 inhibitors is allowed provided any toxicity attributed to prior anti-PD-(L)1-directed therapy did not lead to discontinuation of therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
Key exclusion criteria (21 listed)
- Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior 2 weeks of first dose of study treatment
- History of severe hypersensitivity reactions to other monoclonal antibodies and/or their excipients
- Known presence of neutralizing anti-atezolizumab antibodies (for patients previously treated with atezolizumab)
- Having out of range laboratory values: creatinine, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), absolute neutrophil count (ANC), platelet count, hemoglobin
- Impaired cardiac function or clinically significant cardiac disease, including any of the following:
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 |
|---|---|---|
| AlomfilimabAlso: KY1044, SAR445256A human anti-ICOS monoclonal antibody | Drug | Phase 1: Alomfilimab + Atezolizumab Combination Therapy, Phase 1: Alomfilimab Monotherapy, Phase 2: Alomfilimab + Atezolizumab in Anti-PD-(L)1 Naïve Participants, Phase 2: Alomfilimab + Atezolizumab in Pre-treated Participants |
| AtezolizumabAlso: TECENTRIQAn anti-PD-L1 monoclonal antibody | Drug | Phase 1: Alomfilimab + Atezolizumab Combination Therapy, Phase 2: Alomfilimab + Atezolizumab in Anti-PD-(L)1 Naïve Participants, Phase 2: Alomfilimab + Atezolizumab in Pre-treated Participants |
Primary outcome
Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks
An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. An serious AE (SAE) was any AE that: * resulted in death; * was life-threatening; * resulted in inpatient hospitalization or prolongation of existing hospitalization; * resulted in a persistent or significant disability/incapacity; * resulted in congenital anomaly/birth defect in the offspring of a participant who received IMPs; * constituted an important medical event. Clinically significant changes in laboratory parameters, vital signs and electrocardiogram results were reported as AEs. A TEAE was defined as an AE observed after starting administration of the specific treatment.
Phase 1: Number of Participants Experiencing Dose Changes
Time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks
Dose changes were defined as infusion interruption and dose reduction.
Phase 1: Absolute Dose Intensity
Time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks
Absolute dose intensity was calculated as cumulative dose received (mg) / study treatment duration (weeks).
Phase 1: Relative Dose Intensity
Time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks
Relative dose intensity was calculated as the cumulative dose received (mg) / initial planned cumulative dose (mg). Initial planned cumulative dose was calculated as the starting dose multiplied by the scheduled number of administrations within the study treatment duration.
Phase 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
Time frame: From first dose of study treatment (Day 1) up to 21 days
A DLT was defined as a clinically relevant AE or abnormal laboratory value of Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) ≥ Grade 3 assessed as unrelated to disease, PD, inter-current illness or concomitant medications, which occurs within the first cycle (21 days) of treatment with alomfilimab as single agent or in combination with atezolizumab during the dose escalation part of the study.
Phase 2: Overall Response Rate (ORR) Per RECIST 1.1
Time frame: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 162 weeks
ORR was the percentage of participants with a measurable disease at baseline and with a confirmed response of complete response (CR) or partial response (PR) according to RECIST v1.1 as the best response. The response is confirmed by a later scan conducted at least 4 weeks after the initial response is observed. The 95% confidence interval (CI) was calculated using the exact binomial method (Clopper-Pearson). CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm. All lymph nodes must have been non-pathological in size (< 10mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
15 secondary outcomes
Best Overall Response (BOR) Per RECIST 1.1
Time frame: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively
Progression-free Survival (PFS) Per RECIST 1.1
Time frame: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively
Duration of Response Per RECIST 1.1
Time frame: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively
ORR Per iRECIST
Time frame: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively
PFS Per iRECIST
Time frame: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively
Phase 1: ORR Per RECIST 1.1
Time frame: From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 weeks
Overall Survival Rate at 12 and 24 Months
Time frame: Months 12 and 24
Phase 2: Number of Participants Experiencing TEAEs
Time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 86 weeks
Phase 2: Number of Participants Experiencing Dose Changes
Time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 86 weeks
Phase 2: Absolute Dose Intensity
Time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 86 weeks
Phase 2: Relative Dose Intensity
Time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 86 weeks
Phase 1: Maximum Concentration (Cmax) of Alomfilimab
Time frame: Cycles 1 and 3 Day 1 pre-infusion to 336 hours post-infusion start (21 day cycle length)
Phase 1: Half-life (t1/2) of Alomfilimab
Time frame: Cycles 1 and 3 Day 1 pre-infusion to 336 hours post-infusion start (21 day cycle length)
Number of Participants Experiencing Anti-drug Antibodies (ADA) at Anytime
Time frame: Phase 1: pre-infusion at all cycles (up to 69 cycles) + 90 days SFUP; Phase 2: pre-infusion at all cycles (up to 28 cycles) + 90 day SFUP (21 day cycle length)
Change From Baseline in Tumor-infiltrating Lymphocytes Per mm^2 at Cycle 2 Day 8
Time frame: Baseline and Cycle 2 Day 8 (21 day cycle length)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42259602Naing A, Lin CC, Patel MR, Curigliano G, Burris HA, Thistlethwaite F, De Braud F, Minchom A, Ascierto PA, Wake M, Nguyen MA, Abbadessa G, Sainson RCA, Palu CC, Quaratino S, Deantonio C. First-in-human, phase 1, open-label study of alomfilimab, an anti-ICOS antibody, as a single agent and in combination with anti-PD-L1 in advanced malignancies. J Immunother Cancer. 2026 Jun 8;14(6):e013540. doi: 10.1136/jitc-2025-013540.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at https://vivli.org
Related trials for Squamous Cell Carcinoma of Head and Neck
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 2
Testing the Addition of Chemotherapy or Chemo-Immunotherapy to the Usual Surgery for Advanced Head and Neck Cancer
Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
RecruitingPhase 2
A Study Investigating Alternate Schedules of Tislelizumab Plus Chemotherapy in Japanese Patients With First-line Advanced ESCC
Advanced Esophageal Squamous Cell Carcinoma, Metastatic Esophageal Squamous Cell Carcinoma
RecruitingPhase 2
Testing Whether Cemiplimab (REGN2810) Plus CDX-1140 Given Prior to Surgery Are Better Than Cemiplimab (REGN2810) Alone in Patients With Stage III-IV Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma
RecruitingObservational study
Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing
Solid Tumor, Adult, Colorectal Cancer
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.
Clinical Sciences & Operations study director
Sanofi
22 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Alomfilimab and Atezolizumab in people with Squamous Cell Carcinoma of Head and Neck and Non-small Cell Lung Cancer, run by Kymab Limited at 22 sites in 6 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 16 inclusion and 21 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: stopped early, as of the sponsor's last update on 2 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 22 sites in Italy, United States, United Kingdom, Hungary, Taiwan and 1 more country. 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 2 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?
Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) (time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks). The study lists 6 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 NCT03829501, which also lists 1 linked publication.
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 2 Apr 2025.