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:

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
SasanlimabSub-Study B
AxitinibSub-Study B
SEA-TGTSub-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

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
Sub-Study BExperimentalSasanlimab 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