Study of Denikitug (GS-1811) Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors

Official title

A Phase 1 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Denikitug (GS-1811), an Afucosylated Anti-CCR8 Monoclonal Antibody, as Monotherapy and in Combination With an Anti-PD-1 Monoclonal Antibody in Adults With Advanced Solid Tumors

Overview

This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of denikitug (also known as GS-1811) as monotherapy and in combination with zimberelimab in participants with advanced solid tumors. This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D: combination therapy, and Part F for both monotherapy and combination therapy) in participants with advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or in participants with select solid tumors.

Detailed description

Part D allocation for 1 cohort will be randomized.

Interventions

• Drug Denikitug
  Administered Intravenously
• Drug Zimberelimab
  Administered Intravenously

Primary outcome measures

• Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Part A and C [Time frame: Day 1 Through Day 21]
• Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [Time frame: First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days]
• Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0 [Time frame: First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days]

Secondary outcome measures (10)

• Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for Denikitug [Time frame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days]
• PK Parameter: Minimum Observed Concentration (Cmin) for Denikitug [Time frame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days]
• PK Parameter: Time of Maximum Observed Concentration (Tmax) for Denikitug [Time frame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days]
• PK Parameter: Area Under the Concentration-time Curve (AUC) for Denikitug [Time frame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days]
• Percentage of Participants who Developed Antidrug Antibody (ADA) Against Denikitug [Time frame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days]
• Objective response rate (ORR) in Part D [Time frame: Day 1 Up to End of Treatment (24 months)]
• Disease control rate (DCR) [Time frame: Day 1 Up to End of Treatment (24 months)]
• Time to response (TTR) [Time frame: Day 1 Up to End of Treatment (24 months)]
• Duration of response (DOR) [Time frame: Day 1 Up to End of Treatment (24 months)]
• Progression-free survival (PFS) [Time frame: Day 1 Up to End of Treatment (24 months)]

Eligibility criteria

Inclusion criteria

• Disease:

• Part A: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
• Part B: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
• Part C: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or whose disease is indicated for anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-\[L\]1) monoclonal antibody monotherapy.
• Part D: Individuals with pathologically confirmed select advanced solid tumors.
• Part E: Individuals with pathologically confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit.
• Part F: Individuals with pathologically-confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatments known to confer clinical benefit; or, for participants who will undergo combination therapy, have disease which is indicated for anti-PD-(L)1 mAb monotherapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F.
• Adequate organ function.
• Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.
• Tissue requirement:

• Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample prior to enrollment.
• Part B and select participants in Parts C and F: Must have fresh pre-treatment and on-treatment biopsies for biomarker analysis.

Exclusion criteria

• Concurrent anticancer treatment.
• Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14 days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21 days).
• Any prior CCR8 directed therapy.
• Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed.
• Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected carcinoma in situ, localized prostate cancer, or superficial bladder cancer after undergoing potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease-free for > 2 years.
• History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy.
• History of autoimmune disease or active autoimmune disease requiring systemic treatment within 2 years.
• History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
• Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires IV antibiotics.
• Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
• Positive serum pregnancy test or breastfeeding female.
• Live vaccines within 30 days prior to first dose.
• Significant cardiovascular disease.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 10 centers

• University of California San Diego — La Jolla
• Stanford Cancer Center — Palo Alto
• Smilow Cancer Center — New Haven
• Beth Israel Deaconess Medical Center — Boston
• Tennessee Oncology, PLLC — Nashville
• University of Texas Southwestern Medical Center — Dallas
• Sarah Cannon Research Institute at Mary Crowley — Dallas
• MD Anderson Cancer Center — Houston
• … and 2 more centers

Taiwan · 7 centers

• Changhua Christian Hospital — Changhua
• Chi Mei Hospital, Liouying — Tainan
• National Taiwan University Cancer Center (NTUCC) — Taipei
• National Taiwan University Hospital — Taipei
• Taipei Tzu Chi General Hospital — Taipei
• Taipei Veterans General Hospital — Taipei
• Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital — Taoyuan City

Spain · 5 centers

• Hospital Universitari Vall d´Hebrón — Barcelona
• MD Anderson Cancer Center — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitario Quironsalud Madrid — Madrid
• Clinica Universidad de Navarra — Pamplona

Australia · 3 centers

• Chris O'Brien Lifehouse — Camperdown
• Monash Medical Centre — Clayton
• Peter MacCallum Cancer Centre — Melbourne

Canada · 1 center

• University Health Network, Princess Margaret Cancer Centre — Toronto

Identifiers

NCT: NCT05007782 · GS-US-570-6015 · 2022-501684-40

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗