GB1275 Monotherapy and in Combination With an Anti-PD1 Antibody in Patients With Specified Advanced Solid Tumors or in Combination With Standard of Care in Patients With Metastatic Pancreatic Adenocarcinoma

Sponsor
GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT04060342
Collaborator
Merck Sharp & Dohme LLC (Industry)
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Study Details

Study Description

Brief Summary

This first-in-human (FIH ) study is an open-label, multicenter study that consists of a Phase 1 Dose Escalation/Expansion phase of GB1275 monotherapy or in combination with Anti-PD-1 Antibody or in combination with Standard of Care in Patients with Metastatic Pancreatic Adenocarcinoma followed by a Phase 2 Basket Expansion phase in Patients with Specified Metastatic Solid Tumors

Detailed Description

Note: The Phase 2 portion of the study was not initiated.

Study Design

Study Type:
Interventional
Actual Enrollment :
61 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Phase 1 - Dose Escalation of 3 different Regimens and Expansion, Phase 2 - Basket Expansion of 3 CohortsPhase 1 - Dose Escalation of 3 different Regimens and Expansion, Phase 2 - Basket Expansion of 3 Cohorts
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, First-in-Human, Open-label, Dose Escalation Study of GB1275 Monotherapy and in Combination With an Anti-PD-1 Antibody in Patients With Specified Advanced Solid Tumors or in Combination With Standard of Care in Patients With Metastatic Pancreatic Adenocarcinoma, Followed by Basket Expansion of GB1275 With Standard of Care or in Combination With an Anti-PD-1 Antibody in Patients With Specified Metastatic Solid Tumors
Actual Study Start Date :
Aug 13, 2019
Actual Primary Completion Date :
Apr 11, 2022
Actual Study Completion Date :
Apr 11, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1: Regimen A - GB1275 monotherapy

GB1275 Monotherapy dose escalation: Oral administration. Twice per day (BID).

Drug: GB1275
Oral
Other Names:
  • Investigational
  • Experimental: Phase 1: Regimen B - GB1275 with an Anti-PD-1

    GB1275 with pembrolizumab dose escalation and expansion: GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W).

    Drug: GB1275
    Oral
    Other Names:
  • Investigational
  • Drug: pembrolizumab
    IV infusion
    Other Names:
  • Anti-PD-1
  • Experimental: Phase 1: Regimen C - GB1275 with Standard of Care (SOC)

    GB1275 with SOC dose escalation: GB1275 oral administration; twice per day (BID), and nab-paclitaxel and gemcitabine per United States Prescribing Information (USPI)

    Drug: GB1275
    Oral
    Other Names:
  • Investigational
  • Drug: nab-paclitaxel and gemcitabine
    IV infusion
    Other Names:
  • Abraxane and Gemzar
  • Experimental: Phase 2: Cohort 1 - GB1275 with SOC

    GB1275 with SOC Basket Cohort in patients with newly diagnosed metastatic pancreatic cancer: GB1275 oral administration; twice per day (BID) and nab-paclitaxel and gemcitabine per USPI.

    Drug: GB1275
    Oral
    Other Names:
  • Investigational
  • Drug: nab-paclitaxel and gemcitabine
    IV infusion
    Other Names:
  • Abraxane and Gemzar
  • Experimental: Phase 2: Cohort 2 - GB1275 with an Anti-PD-1

    GB1275 with pembrolizumab Basket Cohort in patients with MSS colorectal cancer: GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W).

    Drug: GB1275
    Oral
    Other Names:
  • Investigational
  • Drug: pembrolizumab
    IV infusion
    Other Names:
  • Anti-PD-1
  • Experimental: Phase 2: Cohort 3 - GB1275 with an Anti-PD-1

    GB1275 with pembrolizumab Basket Cohort in patients with gastric/GEJ cancer, PD-L1 positive: GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W).

    Drug: GB1275
    Oral
    Other Names:
  • Investigational
  • Drug: pembrolizumab
    IV infusion
    Other Names:
  • Anti-PD-1
  • Outcome Measures

    Primary Outcome Measures

    1. Phase 1 Dose Escalation - Regimens A, B,and C: Incidence of dose limiting toxicities (DLTs) [Regimen A and B dose escalation Days 1-21, Regimen C dose escalation Days 8-36 days]

    2. Phase 1 Dose Escalation - Regimens A, B, and C and Phase 1 Expansion - Regimen B: Incidence of adverse events (AEs) [Regimen A and C from first dose through 30 days post last dose, Regimen B from first dose through 90 days post last dose]

    3. Phase 1 Dose Escalation - Regimens A and B: Cmax of GB1275 [From first dose through 30 days post last dose]

      Maximum observed plasma concentration

    4. Phase 1 Dose Escalation - Regimens A and B: Ctrough of GB1275 [From first dose through 30 days post last dose]

      Trough observed plasma concentration

    5. Phase 1 Dose Escalation - Regimens A and B: Tmax of GB1275 [From first dose through 30 days post last dose]

      Time of maximum observed plasma concentration

    6. Phase 1 Dose Escalation - Regimens A and B: t1/2 of GB1275 [From first dose through 30 days post last dose]

      Terminal phase elimination half-life

    7. Phase 1 Dose Escalation - Regimens A and B: AUC of GB1275 [From first dose through 30 days post last dose]

      Area under the plasma concentration-time curve

    8. Phase 1 Dose Escalation - Regimens A and B: CL/F of GB1275 [From first dose through 30 days post last dose]

      Oral clearance

    9. Phase 2 - Basket Cohorts 1, 2 and 3: Objective Response Rate (ORR) [24 months]

      ORR defined as the proportion of subjects with best overall confirmed response (BOCR) of either a complete response (CR) or partial response (PR) as assessed by the Investigator based on RECIST v1.1

    Secondary Outcome Measures

    1. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Cmax of GB1275 [From first dose through 30 days post last dose]

      Maximum observed plasma concentration

    2. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Ctrough of GB1275 [From first dose through 30 days post last dose]

      Trough observed plasma concentration

    3. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Tmax of GB1275 [From first dose through 30 days post last dose]

      Time of maximum observed plasma concentration

    4. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: t1/2 of GB1275 [From first dose through 30 days post last dose]

      Terminal phase elimination half-life

    5. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: AUC of GB1275 [From first dose through 30 days post last dose]

      Area under the plasma concentration-time curve

    6. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: CL/F of GB1275 [From first dose through 30 days post last dose]

      Oral clearance

    7. Phase 1 - Regimen C: Cmax of nab-paclitaxel and gemcitabine [From first dose through 30 days post last dose]

      Maximum observed plasma concentration

    8. Phase 1 - Regimen C: Tmax of nab-paclitaxel and gemcitabine) [From first dose through 30 days post last dose]

      Time of maximum observed plasma concentration

    9. Phase 1 - Regimen C: AUC of nab-paclitaxel and gemcitabine [From first dose through 30 days post last dose]

      Area under the plasma concentration-time curve

    10. Phase 2 - Basket Cohorts 1, 2, and 3: Duration of Response (DOR) [24 months]

      DOR defined as time from date of objective response to first documented date of disease progression or death

    11. Phase 2 - Basket Cohorts 1, 2, and 3: Time to Response (TTR) [24 months]

      TTR defined as time from first dose to first date of objective response

    12. Phase 2 - Basket Cohorts 1, 2, and 3: Clinical Benefit Rate (CBR) [6 months]

      CBR defined as proportion of subjects with confirmed CR, PR, or stable disease (SD) at six months.

    13. Phase 2 - Basket Cohorts 1, 2, and 3: Progression Free Survival (PFS) [24 months]

      PFS defined as time from first dose to first documented date of disease progression or death.

    14. Phase 2 - Basket Cohorts 1, 2, and 3: Time to Progression (TTP) [24 months]

      TTP defined as time from first dose to first documented date of disease progression.

    15. Phase 2 - Basket Cohorts 1, 2, and 3: Overall Survival (OS) [24 months]

      OS defined as time from first dose to date of death.

    16. Phase 2 - Basket Cohorts 1, 2, and 3: Incidence of AEs [Basket Cohorts 1 from first dose through 30 days post last dose, Basket Cohorts 2 and 3 from first dose through 90 days post last dose.]

    17. Phase 2 - Basket Cohort 1, 2 and 3: PK profile of GB1275 [Basket Cohorts 1, 2, and 3 from first dose through 30 days post last dose.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Subject has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

    • Women of childbearing potential must use an acceptable method of contraception

    Phase 1

    Subjects with the the following:
    • Regimen A and B:

    • pancreatic adenocarcinoma,

    • esophageal adenocarcinoma, or esophageal squamous cell carcinoma, or

    • gastric/gastroesophageal junction adenocarcinoma, or

    • TNBC, or

    • prostate cancer, or

    • colorectal adenocarcinoma, or subjects with tumor types that have progressed after receiving initial treatment benefit rom the last single agent checkpoint inhibitor that is approved for the indication or in combination with standard of care therapy, for example, non-small cell lung cancer, small cell lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma, renal cell carcinoma, and hepatocellular carcinoma, etc.

    • Regimen C: newly diagnosed stage IV pancreatic cancer

    Phase 2

    • Cohort 1: pancreatic cancer.

    • Cohort 2: colorectal cancer

    • Cohort 3: gastric/GEJ adenocarcinoma

    Exclusion Criteria:
    • History of another malignancy within 2 years prior to first study drug(s) administration, unless the malignancy was treated with curative intent and the likelihood of relapse is <5% in 2 years

    • Pregnant or nursing

    • Known history of testing positive for human immunodeficiency virus (HIV)

    • Gastrointestinal (GI) tract disease causing the inability to take oral medication.

    • Positive test for Hepatitis B virus surface antigen (HBsAg) or a and/or positive Hep C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection.

    Other protocol-defined inclusion/exclusion criteria will apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCSF Medical Center at Mission Bay San Francisco California United States 94158
    2 University of Colorado Hospital, Anschutz Cancer Pavilion (ACP) Aurora Colorado United States 80045
    3 Washington University School of Medicine - Siteman Cancer Center Saint Louis Missouri United States 63110
    4 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    5 Duke University Medical Center Durham North Carolina United States 27710
    6 The Sarah Cannon Research Institute/Tennessee Oncology Nashville Tennessee United States 37203
    7 South Texas Accelerated Research Therapeutics, LLC San Antonio Texas United States 78229
    8 The Royals Marsden NHS Foundation Trust Sutton Surrey United Kingdom SM2 5PT

    Sponsors and Collaborators

    • GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
    • Merck Sharp & Dohme LLC

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
    ClinicalTrials.gov Identifier:
    NCT04060342
    Other Study ID Numbers:
    • GB1275-1101 (KEYNOTE-A36)
    First Posted:
    Aug 19, 2019
    Last Update Posted:
    Aug 18, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 18, 2022