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

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)

Sponsors

Lead Sponsor: Pfizer

Source Pfizer
Brief Summary

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.

Overall Status Not yet recruiting
Start Date October 22, 2020
Completion Date November 27, 2024
Primary Completion Date November 27, 2024
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Percentage of participants with Dose-limiting toxicities (DLT) First dose (Cycle 1 Day 1) to end of first treatment cycle (about 21-28 days)
Durable Objective Response Rate - Percentage of Participants With Objective Response First dose (Cycle 1 Day 1) to End of Study Treatment (up to about 24 months); each cycle is about 28 days
Secondary Outcome
Measure Time Frame
Number of participants with Treatment-Emergent Adverse Events First dose (Cycle 1 Day 1) to 30 days after last dose (up to about 24 months); each cycle is about 28 days
Percentage of participants with Treatment-Emergent Adverse Events First dose (Cycle 1 Day 1) to 30 days after last dose (up to about 24 months); each cycle is about 28 days
Number of Participants with Treatment-Emergent Laboratory Abnormalities First dose (Cycle 1 Day 1) to 30 days after last dose (up to about 24 months); each cycle is about 28 days
Percentage of Participants with Treatment-Emergent Laboratory Abnormalities First dose (Cycle 1 Day 1) to 30 days after last dose (up to about 24 months); each cycle is about 28 days
Durable Objective Response Rate - Percentage of Participants With Objective Response First dose (Cycle 1 Day 1) to End of Study Treatment (up to about 24 months); each cycle is about 28 days
Objective Response Rate-Percentage of Participants with Objective Response First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months); each cycle is about 28 days
Duration of Response (DR) First objective response to progressive disease or death (up to about 24 months); each cycle is about 28 days
Time to Tumor Response (TTR) First dose (Cycle 1 Day 1) up to first objective response. Each cycle is about 28 days
Progression-Free Survival (PFS) First dose (Cycle 1 Day 1) to progressive disease or death (up to about 24 months). Each cycle is about 28 days
Overall Survival First dose (Cycle 1 Day 1) to death (up to about 40 months); each cycle is about 28 days
Incidence of Anti-Drug Antibody (ADA) for sasanlimab First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months); each cycle is about 28 days
Neutalizing antibody (NAb) titers for sasanlimab First dose (Cycle 1 Day 1) to End of Treatment (up to about 24 months); each cycle is about 28 days
Correlation between Objective Response and PD-L1 expression at baseline First dose (Cycle 1 Day 1) to End of Study Treatment (up to about 24 months); each cycle is about 28 days
PK Parameter AUC (Area Under the Curve) 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
PK Parameter Ctrough 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
PK Parameter Cmax (Maximum Observed Plasma Concentration) 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
PK Parameter Tmax (Time to Reach Maximum Observed Plasma Concentration) 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
Enrollment 375
Condition
Intervention

Intervention Type: Drug

Intervention Name: Sasanlimab Prefillled syringe

Description: prefilled syringe

Arm Group Label: Sub-Study A

Intervention Type: Drug

Intervention Name: Encorafenib

Description: capsules

Arm Group Label: Sub-Study A

Intervention Type: Drug

Intervention Name: Binimetinib

Description: tablets

Arm Group Label: Sub-Study A

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Pfizer CT.gov Call Center Study Director Pfizer
Overall Contact

Last Name: Pfizer CT.gov Call Center

Phone: 1-800-718-1021

Email: [email protected]

Location
Facility: California Cancer Associates for Research and Excellence, Inc (cCARE)
Location Countries

United States

Verification Date

October 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Sub-Study A

Type: Experimental

Description: 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.

Patient Data Yes
Study Design Info

Allocation: Non-Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov