study of gs-0201 alone and in combination in participants with advanced solid tumors

Conditions: Advanced Solid Tumors

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


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