Study to Evaluate the Safety and Tolerability of GS-1811 as Monotherapy and in Combination With Zimberelimab in Adults With Advanced Solid Tumors

Sponsor

Gilead Sciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05007782

Collaborator

(none)

158

Enrollment

Locations

Arms

41.5

Anticipated Duration (Months)

22.6

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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 GS-1811 as monotherapy and in combination with Zimberelimab in participants with advanced solid tumors.

This study will be conducted in 4 parts (Part A and Part B: monotherapy, Part C and Part D:

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor	Drug: GS-1811 Drug: Zimberelimab	Phase 1

Detailed Description

Part D allocation for 1 cohort will be randomized.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

158 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of 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

Actual Study Start Date :

Aug 18, 2021

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A - GS-1811 Dose Escalation	Drug: GS-1811 Administered intravenously
Experimental: Part B - Mandatory Paired Tumor Biopsy	Drug: GS-1811 Administered intravenously
Experimental: Part C: GS-1811 + Zimberelimab dose escalation	Drug: GS-1811 Administered intravenously Drug: Zimberelimab Administered intravenously
Experimental: Part D: GS-1811 + Zimberelimab dose expansion	Drug: GS-1811 Administered intravenously Drug: Zimberelimab Administered intravenously

Outcome Measures

Primary Outcome Measures

Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) [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 [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 [First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days]

Secondary Outcome Measures

Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for GS-1811 [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 GS-1811 [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 GS-1811 [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 GS-1811 [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 GS-1811 [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) [Day 1 Up to End of Treatment (24 months)]
Objective response rate is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Disease control rate (DCR) [Day 1 Up to End of Treatment (24 months)]
Disease control rate is defined as the proportion of participants who achieve CR, PR, or stable disease (SD) as assessed by RECIST Version 1.1
Time to response (TTR) [Day 1 Up to End of Treatment (24 months)]
Time to response is defined as the time from the first dose of GS-1811 in combination with Zimberelimab to the first documentation of CR or PR that is subsequently confirmed
Duration of response (DOR) [Day 1 Up to End of Treatment (24 months)]
Duration of response is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive progressive disease (PD) or death from any cause, if applicable.
Progression-free survival (PFS) [Day 1 Up to End of Treatment (24 months)]
Progression-free survival is defined as the time from the first dose of GS-1811 in combination with Zimberelimab to the earlier of the first documentation of definitive PD or death from any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 treatment known to confer clinical benefit or whose disease is indicated for anti-PD-(L)1 monoclonal antibody monotherapy
Part D: Individuals with pathologically confirmed select advanced solid tumors.
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 Part D
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:
Part A, Part C, and Part D: Must provide pre-treatment adequate tumor tissue sample prior to enrolment
Part B: Must have fresh pre-treatment and on-treatment biopsy 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
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Center	Palo Alto	California	United States	94305
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
3	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
4	Mary Crowley Cancer Research	Dallas	Texas	United States	75230
5	MD Anderson Cancer Center	Houston	Texas	United States	77030
6	NEXT Oncology	San Antonio	Texas	United States	78229
7	University of Wisconsin Clinical Sciences Center	Madison	Wisconsin	United States	53705

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Gilead Clinical Trials Website

Publications

None provided.

Responsible Party:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT05007782

Other Study ID Numbers:

GS-US-570-6015

First Posted:

Aug 16, 2021

Last Update Posted:

Aug 22, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Neoplasms

Study Results

No Results Posted as of Aug 22, 2022