Clinical Trials/NCT05007782

NCT05007782

Recruiting

Phase 1

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

Gilead Sciences25 sites in 5 countries416 target enrollmentAugust 18, 2021

ConditionsAdvanced Solid Tumor

InterventionsZimberelimab Denikitug

DrugsDenikitug Zimberelimab

Overview

Phase: Phase 1
Intervention: Zimberelimab
Conditions: Advanced Solid Tumor
Sponsor: Gilead Sciences
Enrollment: 416
Locations: 25
Primary Endpoint: Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0
Status: Recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

August 18, 2021

End Date

December 1, 2028

Last Updated

4 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Gilead Sciences

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

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).

Arms & Interventions

Part D: Denikitug + Zimberelimab Dose Expansion

Intervention: Zimberelimab

Part E: Denikitug Monotherapy Dose Expansion

Intervention: Denikitug

Part A - Denikitug Dose Escalation

Intervention: Denikitug

Part B - Mandatory Paired Tumor Biopsy

Intervention: Denikitug

Part C: Denikitug + Zimberelimab Dose Escalation

Intervention: Denikitug

Part C: Denikitug + Zimberelimab Dose Escalation

Intervention: Zimberelimab

Part D: Denikitug + Zimberelimab Dose Expansion

Intervention: Denikitug

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

Intervention: Denikitug

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

Intervention: Zimberelimab

Outcomes

Primary Outcomes

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

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 Dose Limiting Toxicities (DLTs) in Part A and C

Time Frame: Day 1 Through Day 21

Secondary Outcomes

Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for Denikitug(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(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(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(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(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(Day 1 Up to End of Treatment (24 months))
Disease control rate (DCR)(Day 1 Up to End of Treatment (24 months))
Time to response (TTR)(Day 1 Up to End of Treatment (24 months))
Duration of response (DOR)(Day 1 Up to End of Treatment (24 months))
Progression-free survival (PFS)(Day 1 Up to End of Treatment (24 months))