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2019-01-28
2024-10-03
2024-10-03
222
NCT03829501
Kymab Limited
Kymab Limited
INTERVENTIONAL
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, 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.
N/A
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2019-01-17 | 2025-01-30 | 2025-03-13 |
2019-02-01 | 2025-03-13 | 2025-04-02 |
2019-02-04 | 2025-04-02 | 2025-03 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Non Randomized
Interventional Model:
Sequential
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: Phase 1: Alomfilimab Monotherapy Participants will receive alomfilimab 0.8 to 240 mg as a single agent via intravenous (IV) infusion every 3 weeks (Q3W). | DRUG: Alomfilimab
|
| EXPERIMENTAL: Phase 1: Alomfilimab + Atezolizumab Combination Therapy Participants will receive alomfilimab 2.4 to 80 mg in combination with atezolizumab 1200 mg via IV infusion Q3W. | DRUG: Alomfilimab
DRUG: Atezolizumab
|
| EXPERIMENTAL: Phase 2: Alomfilimab + Atezolizumab in Anti-PD-(L)1 Naïve Participants 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. | DRUG: Alomfilimab
DRUG: Atezolizumab
|
| EXPERIMENTAL: Phase 2: Alomfilimab + Atezolizumab in Pre-treated Participants 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. | DRUG: Alomfilimab
DRUG: Atezolizumab
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| 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. | 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. | 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). | 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. | 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. | 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. | From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 162 weeks |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| 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). | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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. | 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. | 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. | 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. | 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. | Baseline and Cycle 2 Day 8 (21 day cycle length) |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
