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Trial record 1 of 1 for:    B8011011
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Umbrella Study of Sasanlimab Combined With Targeted Therapies in Participants With Non Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT04585815
Recruitment Status : Recruiting
First Posted : October 14, 2020
Last Update Posted : August 18, 2021
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Sasanlimab Prefillled syringe Drug: Encorafenib Drug: Binimetinib Drug: Sasanlimab Drug: Axitinib Drug: SEA-TGT Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 375 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 10, 2020
Estimated Primary Completion Date : November 27, 2024
Estimated Study Completion Date : January 17, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sub-Study A
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.
Drug: Sasanlimab Prefillled syringe
prefilled syringe

Drug: Encorafenib
capsules

Drug: Binimetinib
tablets

Experimental: Sub-Study B
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.
Drug: Sasanlimab
solution supplied in vials

Drug: Axitinib
tablets

Drug: SEA-TGT
solution in vials




Primary Outcome Measures :
  1. 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) ]
    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.

  2. 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 ]
    Sub-Study A only, Phase 2 only: Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) lasting for at lease 10 months, according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

  3. 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 21 days ]
    Sub-Study B only, Phase 2 only: Percentage of participants with CR or PR, according to RECIST v1.1.


Secondary Outcome Measures :
  1. 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 ]
    Phase 1b and Phase 2

  2. 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 ]
    Phase 1b and Phase 2

  3. 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 ]
    Phase 1b and Phase 2

  4. 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 ]
    Phase 1b and Phase 2

  5. 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 ]
    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

  6. 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 ]
    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.

  7. 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 ]
    Phase 2 only

  8. 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 ]
    Phase 2 only: The time from first dose to first documentation of objective tumor response of CR or PR.

  9. 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 ]
    Phase 2 only

  10. 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 ]
    Phase 2 only

  11. 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 ]
    Phase 1b and Phase 2

  12. 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 ]
    Sub-Study A only, Phase 1b and Phase 2

  13. 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. ]
    Phase 2 only

  14. 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. ]
    Phase 1b and Phase 2: Ctrough of the study drugs when administered in combination, as data permit.

  15. 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 ]
    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.

  16. 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 ]
    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.

  17. 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 ]
    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.

  18. 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 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04585815


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
Show Show 52 study locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04585815    
Other Study ID Numbers: B8011011
2020-002829-28 ( EudraCT Number )
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: August 18, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
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
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Axitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action