Testing GS-0201 alone and with another drug in patients with advanced solid tumors

A Phase 1 Study to Evaluate the Safety and Tolerability of GS-0201 as Monotherapy and in Combination in Adults With Advanced Solid Tumors

This study is testing a new drug called GS-0201, alone and with another drug, to see if it’s safe and how much of it can be given to people with advanced solid tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 254 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Gilead Sciences (Industry-sponsored)
• Drugs / interventions: Chemotherapy, Immunotherapy, radiation, prednisone, sacituzumab
• Locations: 7 sites (Boston, Massachusetts and 6 other locations)
• Trial ID: NCT06167317 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and dosing of GS-0201, both as a standalone treatment and in combination with sacituzumab govitecan, in patients suffering from advanced solid tumors. The study is designed to determine the maximum tolerated dose and the recommended dose for further phases of treatment. Participants will undergo assessments to ensure they meet specific health criteria and will provide tumor tissue samples for analysis. The trial is in its first phase, focusing on establishing safety and tolerability.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with measurable advanced solid tumors and adequate organ function.

Not a fit: Patients with non-measurable disease or those who do not meet the organ function requirements may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination is being evaluated for the first time.

Eligibility 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 21 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

Where this trial is running

Boston, Massachusetts and 6 other locations

• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• NEXT Austin — Austin, Texas, United States (Recruiting)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• NEXT Dallas — Irving, Texas, United States (Recruiting)
• Rambam Health Care Campus — Haifa, Israel (Recruiting)
• Tel Aviv Sourasky Medical Center — Tel Aviv, Israel (Recruiting)
• Chaim Sheba Medical Center — Tel Litwinsky, Israel (Recruiting)

Study contacts

• Study coordinator: Gilead Clinical Study Information Center

Conditions Advanced Solid Tumors