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

Gilead Sciences

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Zimberelimab; Drug: Denikitug

Study type: Interventional

Funder types: Industry

Identifiers

NCT05007782

2022-501684-40 (Other Identifier)

GS-US-570-6015

Details and patient eligibility

About

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.

Full description

Part D allocation for 1 cohort will be randomized.

Enrollment: 416 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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416 participants in 6 patient groups

Part A - Denikitug Dose Escalation

Experimental group

Treatment:

Drug: Denikitug

Part B - Mandatory Paired Tumor Biopsy

Experimental group

Treatment:

Drug: Denikitug

Part C: Denikitug + Zimberelimab Dose Escalation

Experimental group

Treatment:

Drug: Denikitug

Drug: Zimberelimab

Part D: Denikitug + Zimberelimab Dose Expansion

Experimental group

Treatment:

Drug: Denikitug

Drug: Zimberelimab

Part E: Denikitug Monotherapy Dose Expansion

Experimental group

Treatment:

Drug: Denikitug

Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and Schedule

Experimental group

Treatment:

Drug: Denikitug

Drug: Zimberelimab