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

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05007782
• Other study ID #: GS-US-570-6015
• Secondary ID: 2022-501684-40
• Status: Recruiting
• Phase: Phase 1
• Start date: August 18, 2021
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: Gilead Sciences
• Contact: Gilead Clinical Study Information Center
• Phone: 1-833-445-3230 (GILEAD-0)
• Email: GileadClinicalTrials[@]gilead.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Description:

Part D allocation for 1 cohort will be randomized.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 376
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• GS-1811
Administered Intravenously
• Zimberelimab
Administered Intravenously

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Canada	University Health Network, Princess Margaret Cancer Centre	Toronto
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Quironsalud Madrid	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Chi Mei Hospital, Liouying	Tainan City
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Taipei Tzu Chi General Hospital	Taipei City
Taiwan	Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital	Taoyuan City
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of California San Diego	La Jolla	California
United States	University of Wisconsin Clinical Sciences Center	Madison	Wisconsin
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Smilow Cancer Center	New Haven	Connecticut
United States	Stanford Cancer Center	Palo Alto	California
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Part A and C		Day 1 Through Day 21
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Objective response rate (ORR) in Part D	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	Day 1 Up to End of Treatment (24 months)
Secondary	Disease control rate (DCR)	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	Day 1 Up to End of Treatment (24 months)
Secondary	Time to response (TTR)	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	Day 1 Up to End of Treatment (24 months)
Secondary	Duration of response (DOR)	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.	Day 1 Up to End of Treatment (24 months)
Secondary	Progression-free survival (PFS)	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	Day 1 Up to End of Treatment (24 months)

External Links

•   Gilead Clinical Trials Website