Study Details

PROTOCOL 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

Participation Requirements

Age

18 Years +

Sex

ALL

Healthy Volunteers

Medical Condition

Advanced Solid Tumors

Gender

N/A

Date

January 2024 - September 2028

Study Type

INTERVENTIONAL

Study Phase

PHASE1

Product

GS-0201, Sacituzumab Govitecan

Eligibility Information

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

Locations

Locations (7)

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02459

NEXT Austin

Austin, Texas, United States, 78758

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

NEXT Dallas

Irving, Texas, United States, 75039

Rambam Health Care Campus

Haifa, Israel, 31096

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 6423906

Chaim Sheba Medical Center

Tel Hashomer, Israel, 52621

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

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