Clinical Trials /

Umbrella Study of Sasanlimab Combined With Targeted Therapies in Participants With Non Small Cell Lung Cancer

NCT04585815

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
Sasanlimab Prefillled syringeSub-Study A
EncorafenibSub-Study A
BinimetinibSub-Study A

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

NameTypeDescriptionInterventions
Sub-Study AExperimentalSasanlimab 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

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

        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.
      
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
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
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
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
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
Safety Issue:
Description:Phase 1b only: Percentage of participants with confirmed CR or PR, 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
Safety Issue:
Description:Phase 1 and Phase 2: 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
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
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
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
Safety Issue:
Description:Phase 2 only
Measure:Incidence of Anti-Drug Antibody (ADA) 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: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:Phase 1b and Phase 2
Measure:Correlation 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
Safety Issue:
Description:Phase 1 and Phase 2
Measure:PK Parameter AUC (Area Under the Curve)
Time Frame:First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months). Day 1, 8, and 15 of Cycle 1. Day 1 of Cycle 2 and 3. Days 1 and 8 of Cycle 5. Day 1 of Cycles 7, 10, 13, and then every 6 cycles until EOT. Each cycle is about 28 days
Safety Issue:
Description:Phase 1b and Phase 2: AUC of sasanlimab, encorafenib, and binimetinib when administered in combination, as data permit. AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Measure:PK Parameter Ctrough
Time Frame:First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months). Day 1, 8, and 15 of Cycle 1. Day 1 of Cycle 2 and 3. Days 1 and 8 of Cycle 5. Day 1 of Cycles 7, 10, 13, and then every 6 cycles until EOT. Each cycle is about 28 days
Safety Issue:
Description:Phase 1b and Phase 2: Ctrough of sasanlimab, encorafenib, and binimetinib when administered in combination, as data permit.
Measure:PK Parameter Cmax (Maximum Observed Plasma Concentration)
Time Frame:First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months). Day 1, 8, and 15 of Cycle 1. Day 1 of Cycle 2 and 3. Days 1 and 8 of Cycle 5. Day 1 of Cycles 7, 10, 13, and then every 6 cycles until EOT. Each cycle is about 28 days
Safety Issue:
Description:Phase 1b and Phase 2: Cmax of sasanlimab, encorafenib, and binimetinib when administered in combination, as data permit.
Measure:PK Parameter Tmax (Time to Reach Maximum Observed Plasma Concentration)
Time Frame:First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months). Day 1, 8, and 15 of Cycle 1. Day 1 of Cycle 2 and 3. Days 1 and 8 of Cycle 5. Day 1 of Cycles 7, 10, 13, and then every 6 cycles until EOT. Each cycle is about 28 days
Safety Issue:
Description:Phase 1b and Phase 2: Tmax of sasanlimab, encorafenib, and binimetinib when administered in combination, as data permit.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • Non-Small-Cell Lung Carcinoma

Last Updated

October 9, 2020