Study of GS-0201 Alone and in Combination in Participants With Advanced Solid Tumors

• Status: Recruiting
• Trial end date: 2028-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The main goal of this first in human (FIH) study is to learn about the safety and dosing of GS-0201 when given alone or in combination with sacituzumab govitecan (SG) in participants with advanced solid tumors.

The primary objectives of this study are to:

• To assess the safety and tolerability of GS-0201 as monotherapy and in combination with SG in participants with selected advanced solid tumors

• To identify the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-0201 as monotherapy and the MTD and/or the RP2D and dosing schedule of GS-0201 in combination with SG in participants with selected advanced solid tumors

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences
• Treatments: Sacituzumab govitecan

Criteria

Inclusion Criteria:

• Able to understand and give written informed consent.

• Assigned female or male at birth, 18 years of age or older.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria by investigator assessment.

• Organ function requirements:

• Adequate hematologic function

• Adequate hepatic function

• Creatinine clearance

• Coagulation

• Tissue requirement:

• Parts A, B, C, and D:

• Pre-treatment tumor tissue is required.

• Parts A and C backfill biopsy cohorts:

• Participants must agree to fresh pre- and on-treatment biopsies.

• Participants assigned male at birth and participants assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception

• Willing and able to comply with the requirements and restrictions in this protocol

• Part A (GS-0201 Monotherapy Dose Escalation) Inclusion Criteria:

• Histologically/cytologically confirmed progressive/advanced solid tumors with selected molecular lesions.

• Participants must have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy

• Part B (Dose Expansion) Inclusion Criteria:

• Disease documented as:

• Cohort B1:

• Histologically or cytologically confirmed progressive/advanced selected solid tumor diagnoses harboring defined molecular lesions

• Participants may potentially be required to forgo treatment with approved agent(s) to be able to participate in the study

• Cohort B2:

• Histologically or cytologically confirmed progressive/advanced solid tumor diagnoses harboring defined molecular lesions not included in Cohort B1

• Participants must have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy

• Part C (Dose Escalation) Inclusion Criteria:

• Histologically or cytologically confirmed unresectable locally advanced/metastatic selected solid tumors

• Part D (Dose Expansion) Inclusion Criteria:

• Disease documented as:

• Cohort D1:

• Histologically or cytologically confirmed unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC)

• Cohort D2:

• Histologically or cytologically confirmed unresectable locally advanced or metastatic HR+/HER2- (IHC 0, IHC 1+ or IHC 2+/ in situ hybridization (ISH-)) breast cancer.

Exclusion Criteria:

• Pregnant or lactating females

• Known hypersensitivity to any of the study drugs, its metabolites, or formulation excipients

• Requirement for ongoing therapy with or use of any prohibited medications described in the protocol

• Participants with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with findings suggestive of MDS/AML

• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of GS-0201

• The therapies listed below within the specified timeframe:

• Major surgery (excluding minor procedures, eg, placement of vascular access, gastrointestinal/biliary stent, biopsy) < 4 weeks prior to planned Cycle 1 Day 1

• Immunotherapy or biologic therapy < 21 days prior to planned Cycle 1 Day 1

• Chemotherapy < 14 days prior to planned Cycle 1 Day 1, or < 42 days for mitomycin or nitrosoureas

• Targeted small molecule therapy < 14 days prior to planned Cycle 1 Day 1

• Receipt of experimental therapy within 28 days or 5 experimental treatment half-lives (whichever is longer) prior to planned Cycle 1 Day 1

• Hormonal or other adjunctive therapy for cancers other than the cancer under evaluation in this study that started < 14 days prior to planned Cycle 1 Day 1 are not permitted. Hormonal therapy, bisphosphonates, somatostatin analogues, and leuprolide are permitted if started ≥ 14 days prior to planned Cycle 1 Day 1

• Radiotherapy within 2 weeks prior to planned Cycle 1 Day 1 and the radiation is not administered to a target lesion

• Any prior allogeneic tissue/solid organ transplantation, including allogeneic hematopoietic stem cell transplantation. Participants with a history of autologous hematopoietic stem cell transplantation are also excluded

• Have not recovered (ie, Grade 1 or lower) from AEs due to a previously administered agent

• Prior treatment with approved or experimental prohibited agents as detailed in the protocol.

• Diagnosis of immunodeficiency, either primary or acquired, or requires systemic corticosteroids (> 10 mg of prednisone daily, or equivalent). However, replacement doses, topical, ophthalmologic, and inhalational steroids are permitted

• Have an active second malignancy

• Have known active central nervous system (CNS) metastases

• Participants with carcinomatous meningitis or primary CNS tumors are excluded regardless of clinical stability

• Meet any of the following criteria for cardiac disease:

• Myocardial infarction or unstable angina pectoris within 6 months of enrollment

• History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication)

• QT interval > 470 msec

• New York Heart Association Class III or greater congestive heart failure or known left ventricular ejection fraction less than 40%

• Meet any of the following infectious criteria:

• Have active serious infection requiring antimicrobials

• Have active hepatitis B virus (HBV) or hepatitis C virus (HCV), or HIV. In participants with a history of HBV or HCV, participants with detectable viral loads will be excluded

• Participants who test positive for hepatitis B surface antigen. Participants who test positive for hepatitis B core antibody are eligible with a negative HBV DNA by quantitative Polymerase chain reaction (PCR)

• Participants who test positive for HCV antibody. Participants who test positive for HCV antibody are eligible with a negative HCV RNA by quantitative PCR

• Participants who test positive for HIV antibody

• History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, or radiation pneumonitis requiring steroids

• Symptomatic ascites or pleural effusion

• Have other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations

• Any medical condition that, in the investigator's or sponsor's opinion, poses an undue risk to the participant's participation in the study

• Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation of study drug(s) (inactivated, viral vector vaccines, and messenger RNA (mRNA) vaccines are allowed; seasonal vaccines should be up to date prior to planned Cycle 1 Day 1)

• Parts C (Dose Escalation) and D (Dose Expansion): Combination Cohorts:

• Participants with active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease) and participants with a history of bowel obstruction or gastrointestinal perforation within 6 months prior to planned Cycle 1 Day 1

• Participants who previously received topoisomerase 1 inhibitors or antibody-drug conjugates containing a topoisomerase 1 inhibitor

• Known severe intolerance or life-threatening hypersensitivity reactions to humanized monoclonal antibodies or intravenous (IV) immunoglobulin preparations; any history of anaphylaxis; history of human anti-human antibody response