Clinical trial NCT05840224: Study of GS-4528 in Adults With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2023-05-03
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: First dose date up to 90 days post last dose (Up to 24 months)
measure: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 up to 4 weeks
measure: Maximum Tolerable Dose (MTD) of GS-4528
timeFrame: Day 1 up to 4 weeks
Secondary outcomes:
measure: Pharmacokinetic (PK) parameter: Cmax of GS-4528 as Monotherapy and in Combination With Anti-PD-1 Monoclonal Antibody
timeFrame: Predose on Day 1 and post dose up to end of treatment (EOT, Up to 24 months)
measure: PK parameter: Cmin of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody
timeFrame: Predose on Day 1 and post dose up to EOT (Up to 24 months)
measure: PK parameter: AUC of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody
timeFrame: Predose on Day 1 and post dose up to EOT (Up to 24 months)
measure: Serum Concentrations of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody
timeFrame: Predose on Day 1 and post dose up to EOT (Up to 24 months)
measure: Percentage of Participants who Develop Antidrug Antibody (ADA) Against GS-4528
timeFrame: Predose on Day 1 and post dose up to 60 day follow-up (Up to 24 months)
Other outcomes:
Locations:
city: Seattle
country: United States
facility: The University of Washington/FHCC
state: Washington
city: Ottawa
country: Canada
facility: The Ottawa Hospital
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Cancer Centre
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health Systems
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: NEXT Oncology-Hospital Quironsalud Barcelona - Unidad de Ensayos Fase 1
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron- Oncology Service
city: Madrid
country: Spain
facility: START MADRID_Hospital Universitario Fundacion Jimenez Diaz - Unidad de Ensayos Fases I
city: Madrid
country: Spain
facility: START MADRID_HM Sanchinarro-CIOCC-Unidad de Ensayos Fases I
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra- Unidad Central de Ensayos Clinicos
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital Linkuo Branch of the Chang Gung Medical Foundation
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: