Study of GS-4528 in Adults With Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase 1 Study to Evaluate the Safety and Tolerability of GS-4528 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: NCT05840224
• Other study ID #: GS-US-616-6291
• Secondary ID: 2022-502070-16
• Status: Recruiting
• Phase: Phase 1
• Start date: May 11, 2023
• Est. completion date: December 2025

Study information

• Verified date: June 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

The goals of this clinical study are to identify if GS-4528 alone or in combination with anti-programmed cell death protein 1 (PD-1) (Anti-PD-1) Monoclonal Antibody is safe and tolerable in people with solid tumors and to identify the recommended dose of GS-4528 for further development that is safe to give to people alone or in combination with Anti-PD-1 Monoclonal Antibody. The primary objectives of this study are: - To assess the safety and tolerability of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal Antibody in participants with advanced solid tumors. - To identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and/or the recommended Phase 2 dose (RP2D) of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal Antibody in participants with advanced solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 132
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Documented disease:
• Phase 1a dose escalation and backfill cohorts; Phase 1b dose escalation:

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 have a contraindication to receive the therapy.

• Phase 1a dose expansion: 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 or have a contraindication to receive the therapy.
• Eastern Cooperative Oncology Group performance status 0 or 1.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
• Adequate organ function.
• Individuals of childbearing potential who engage in heterosexual intercourse must agree to use method(s) of contraception.
• Tissue requirements:
• Phase 1a dose escalation, Phase 1a dose expansion, and Phase 1b dose escalation:

Must provide pre-treatment adequate tumor tissue sample prior to enrolment.

• Phase 1a backfill cohorts: Individuals must have fresh pre-treatment and on-treatment biopsy for biomarker analysis.
• Life expectancy = 3 months.

Key Exclusion Criteria:

• Positive serum pregnancy test or lactating female.
• Prohibited concurrent anticancer therapy listed in the protocol.
• Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: major surgery (<28 days), immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14 days or < 5 half-lives whichever is shorter), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21 days).
• Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation.
• Diagnosis of immunodeficiency, either primary or acquired, or systemic steroid requirement of > 10 mg of prednisone or equivalent.
• 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 that has required systemic treatment within 2 years prior to the start of study treatment.
• Concurrent active second malignancy. Note: Individuals with a history of malignancy that have been completely treated, with no evidence of active cancer for 2 years prior to enrollment, or participants with surgically cured tumors with low risk of recurrence are allowed to enroll.
• Have known active central nervous system (CNS) metastases and/ or carcinomatous meningitis.
• Significant cardiovascular disease.
• Have active serious infection requiring antibiotics.
• Have active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
• History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
• Symptomatic ascites or pleural effusion.
• Live vaccines within 28 days of initiation of investigational product(s). Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Biological:
• GS-4528
Administered intravenously

Drug:
• Zimberelimab
Administered intravenously.

Locations

Country	Name	City	State
Canada	The Ottawa Hospital	Ottawa
Canada	University Health Network, Princess Margaret Cancer Centre	Toronto
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health Systems	Seoul
Spain	Hospital Universitari Vall D'Hebron- Oncology Service	Barcelona
Spain	NEXT Oncology-Hospital Quironsalud Barcelona - Unidad de Ensayos Fase 1	Barcelona
Spain	START MADRID_HM Sanchinarro-CIOCC-Unidad de Ensayos Fases I	Madrid
Spain	START MADRID_Hospital Universitario Fundacion Jimenez Diaz - Unidad de Ensayos Fases I	Madrid
Spain	Clinica Universidad de Navarra- Unidad Central de Ensayos Clinicos	Pamplona
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital Linkuo Branch of the Chang Gung Medical Foundation	Taoyuan
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United States	The University of Washington/FHCC	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		First dose date up to 90 days post last dose (Up to 24 months)
Primary	Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)		Day 1 up to 4 weeks
Primary	Maximum Tolerable Dose (MTD) of GS-4528		Day 1 up to 4 weeks
Secondary	Pharmacokinetic (PK) parameter: Cmax of GS-4528 as Monotherapy and in Combination With Anti-PD-1 Monoclonal Antibody	Cmax is defined as the maximum observed concentration of drug.	Predose on Day 1 and post dose up to end of treatment (EOT, Up to 24 months)
Secondary	PK parameter: Cmin of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody	Cmin is defined as the minimum observed concentration of drug.	Predose on Day 1 and post dose up to EOT (Up to 24 months)
Secondary	PK parameter: AUC of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody	AUC is defined as the area under the concentration versus time curve.	Predose on Day 1 and post dose up to EOT (Up to 24 months)
Secondary	Serum Concentrations of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody		Predose on Day 1 and post dose up to EOT (Up to 24 months)
Secondary	Percentage of Participants who Develop Antidrug Antibody (ADA) Against GS-4528		Predose on Day 1 and post dose up to 60 day follow-up (Up to 24 months)

External Links

•   Gilead Clinical Trials Website