Description:
Phase 1b/Phase 2 open-label, multi-center, parallel group umbrella study.
Sasanlimab (a PD-1 antagonist monoclonal antibody) will be combined with a different targeted
therapy in each sub-study. The Phase1b part of each sub-study will evaluate the safety of the
combination and select the dose for the Phase 2 part. The Phase 2 part of each sub-study will
evaluate the anti-tumor activity of the combination.
Title
- Brief Title: Umbrella Study of Sasanlimab Combined With Targeted Therapies in Participants With Non Small Cell Lung Cancer
- Official Title: A Phase 1b/2 Open Label Umbrella Study of Sasanlimab Combined With Anti-Cancer Therapies Targeting Multiple Molecular Mechanisms in Participants With Non-Small Cell Lung Cancer (NSCLC)
Clinical Trial IDs
- ORG STUDY ID:
B8011011
- SECONDARY ID:
2020-002829-28
- NCT ID:
NCT04585815
Conditions
- Carcinoma, Non-Small-Cell Lung
Interventions
Drug | Synonyms | Arms |
---|
Sasanlimab Prefillled syringe | | Sub-Study A |
Encorafenib | | Sub-Study A |
Binimetinib | | Sub-Study A |
Sasanlimab | | Sub-Study B |
Axitinib | | Sub-Study B |
SEA-TGT | | Sub-Study B |
Purpose
Phase 1b/Phase 2 open-label, multi-center, parallel group umbrella study.
Sasanlimab (a PD-1 antagonist monoclonal antibody) will be combined with a different targeted
therapy in each sub-study. The Phase1b part of each sub-study will evaluate the safety of the
combination and select the dose for the Phase 2 part. The Phase 2 part of each sub-study will
evaluate the anti-tumor activity of the combination.
Trial Arms
Name | Type | Description | Interventions |
---|
Sub-Study A | Experimental | Sasanlimab will be administered subcutaneously. Encorafenib & binimetinib will be administered orally. Treatments will be administered until progressive disease, unacceptable AE, participant withdraws, or study is terminated. | - Sasanlimab Prefillled syringe
- Encorafenib
- Binimetinib
|
Sub-Study B | Experimental | Sasanlimab will be administered subcutaneously. Axitinib will be administered orally. SEA-TGT will be administered intravenously. Treatments will be administered until progressive disease, unacceptable AE, patient withdraws, or study is terminated. | - Sasanlimab
- Axitinib
- SEA-TGT
|
Eligibility Criteria
Inclusion Criteria Umbrella Phase 1b & 2:
- Histologically or cytologically confirmed locally advanced/metastatic (Stage IIIB-IV)
NSCLC.
- At least one measurable lesion per RECIST v1.1 at Screening.
- ECOG Performance Status 0 or 1.
- Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
- Adequate hepatic, renal, and bone marrow function.
Additional Inclusion Criteria for Sub-Study A Phase 1b &2:
-BRAFV600E mutation in tumor tissue or plasma as determined by a local laboratory PCR or
NGS assay and documented in a local pathology report.
Additional Inclusion Criteria for Sub-Study A Phase 1b only:
-Any line of therapy for locally advanced/metastatic NSCLC.
Additional Inclusion Criteria for Sub-Study A Phase 2 only:
-Previously untreated for locally advanced/metastatic NSCLC
Additional Inclusion Criteria for Sub-Study B Phase 1b only::
-Any line of therapy for locally advanced/metastatic NSCLC.
Additional Inclusion Criteria for Sub-Study B Phase 2 only:
- Previously untreated for locally advanced/metastatic NSCLC (Arms B1 & B2), or
- One or 2 prior lines of therapy for advanced/metastatic NSCLC (Arm B3), including
immune checkpoint inhibitor treatment + chemotherapy, and have progressed during or
after that therapy.
- PD-L1 TPS ≥1%
Exclusion Criteria Umbrella Phase 1b &2:
- Active or prior autoimmune disease that might deteriorate when receiving an
immunostimulatory agent.
- Active, non-infectious pneumonitis, pulmonary fibrosis, or known history of
immune-mediated pneumonitis.
- Active infection requiring systemic therapy.
- Clinically significant cardiovascular disease.
- Other malignancy within 2 years of first dose, with exceptions.
- Symptomatic brain metastasis, with exceptions.
Additional Exclusion Criteria for Sub-Study A Phase 1b&2:
- EGFR mutation, ALK fusion oncogene, or ROS1 rearrangement.
- Prior treatment with any BRAF inhibitor or MEK inhibitor.
Additional Exclusion Criteria for Sub-Study A Phase 2 only:
-Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.
Additional Exclusion Criteria for Sub-Study B Phase 1b&2:
-Documentation of any tumor-driving molecular alteration (eg, BRAF, EGFR, ALK)
Additional Exclusion Criteria for Sub-Study B Phase 2 only:
- Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.(Arms B1 & B2)
- Confirmed progressive disease on 1st or 2nd imaging tumor assessment after initiation
of therapy for advanced/metastatic NSCLC.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Percentage of participants with Dose-limiting toxicities (DLT) |
Time Frame: | First dose (Cycle 1 Day 1) to end of first treatment cycle (about 21-28 days) |
Safety Issue: | |
Description: | Phase 1 Primary Outcome: DLTs are a predefined set of observed adverse events that are at least possibly related to at least 1 of the investigational agents. |
Secondary Outcome Measures
Measure: | Number of participants with Treatment-Emergent Adverse Events |
Time Frame: | First dose (Cycle 1 Day 1) to 30 days after last dose (up to about 24 months); each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Phase 1b and Phase 2 |
Measure: | Percentage of participants with Treatment-Emergent Adverse Events |
Time Frame: | First dose (Cycle 1 Day 1) to 30 days after last dose (up to about 24 months); each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Phase 1b and Phase 2 |
Measure: | Number of Participants with Treatment-Emergent Laboratory Abnormalities |
Time Frame: | First dose (Cycle 1 Day 1) to 30 days after last dose (up to about 24 months); each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Phase 1b and Phase 2 |
Measure: | Percentage of Participants with Treatment-Emergent Laboratory Abnormalities |
Time Frame: | First dose (Cycle 1 Day 1) to 30 days after last dose (up to about 24 months); each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Phase 1b and Phase 2 |
Measure: | Durable Objective Response Rate - Percentage of Participants With Objective Response |
Time Frame: | First dose (Cycle 1 Day 1) to End of Study Treatment (up to about 24 months); each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Sub-Study A only, Phase 1b only: Percentage of participants with confirmed CR or PR lasting for at lease 10 months, according to RECIST v1.1 |
Measure: | Objective Response Rate-Percentage of Participants with Objective Response |
Time Frame: | First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months); each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Sub-study A Phase 1 and Phase 2, Sub-Study B, Phase 1 only: Percentage of participants with CR or PR, according to RECIST v1.1. |
Measure: | Duration of Response (DR) |
Time Frame: | First objective response to progressive disease or death (up to about 24 months); each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Phase 2 only |
Measure: | Time to Tumor Response (TTR) |
Time Frame: | First dose (Cycle 1 Day 1) up to first objective response. Each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Phase 2 only: The time from first dose to first documentation of objective tumor response of CR or PR. |
Measure: | Progression-Free Survival (PFS) |
Time Frame: | First dose (Cycle 1 Day 1) to progressive disease or death (up to about 24 months). Each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Phase 2 only |
Measure: | Overall Survival |
Time Frame: | First dose (Cycle 1 Day 1) to death (up to about 40 months); each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Phase 2 only |
Measure: | Incidence of Anti-Drug Antibody (ADA) for the study drugs |
Time Frame: | First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months); each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B |
Safety Issue: | |
Description: | Phase 1b and Phase 2 |
Measure: | Neutalizing antibody (NAb) titers for sasanlimab |
Time Frame: | First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months); each cycle is about 28 days |
Safety Issue: | |
Description: | Sub-Study A only, Phase 1b and Phase 2 |
Measure: | Association between Objective Response and PD-L1 expression at baseline |
Time Frame: | First dose (Cycle 1 Day 1) to End of Study Treatment (up to about 24 months); each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B. |
Safety Issue: | |
Description: | Phase 2 only |
Measure: | PK Parameter Ctrough |
Time Frame: | First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months). About 1-3 draws per Cycle for the first year, and then every 6 cycles until EOT. Each cycle is about 28 days in Sub-Study A and 21 days in Sub-Study B. |
Safety Issue: | |
Description: | Phase 1b and Phase 2: Ctrough of the study drugs when administered in combination, as data permit. |
Measure: | European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) Score |
Time Frame: | First dose (Cycle 1 Day 1) to End of Study Treatment (up to about 24 months); each cycle is about 28 days |
Safety Issue: | |
Description: | Sub-Study A only, Phase 2 only; EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. |
Measure: | European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) Score |
Time Frame: | First dose (Cycle 1 Day 1) to End of Study Treatment (up to about 24 months); each cycle is about 28 days |
Safety Issue: | |
Description: | Sub-Study A only, Phase 2 only; QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms. |
Measure: | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) Score |
Time Frame: | First dose (Cycle 1 Day 1) to End of Study Treatment (up to about 24 months); each cycle is about 28 days |
Safety Issue: | |
Description: | Sub-Study A only, Phase 2 only; EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. |
Measure: | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) Score |
Time Frame: | First dose (Cycle 1 Day 1) to End of Study Treatment (up to about 24 months); each cycle is about 28 days |
Safety Issue: | |
Description: | Sub-Study A only, Phase 2 only; QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Pfizer |
Trial Keywords
- Non-Small-Cell Lung Carcinoma
- NSCLC
- non small cell lung cancer
- non-small cell lung cancer
- BRAF mutation
- BRAF V600e
- BRAF
- B-RAF NSCLC
- lung cancer
- immunotherapy
- sasanlimab
- encorafenib
- binimetinib
- axitinib
- SEA-TGT
- TIGIT
- locally advanced
- metastatic
- ECOG 0
- ECOG 1
- Stage 3B
- Stage IV
- previously untreated
- second-line therapy
- first-line therapy
Last Updated
August 18, 2021