IRB Study Number 24-919
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
• To compare the effect of SG relative to TPC on PFS as assessed by BICR
• To compare the effect of SG relative to TPC on OS
Secondary Objectives
• To compare the effect of SG relative to TPC on ORR as assessed by BICR
• To compare the effect of SG relative to TPC on physical function
• To compare the effect of SG relative to TPC on the following:
PFS as assessed by investigator
ORR as assessed by investigator
DOR as assessed by BICR and investigator
CBR as assessed by BICR and investigator
• To evaluate safety and tolerability of SG relative to TPC
• To compare the effect of SG relative to TPC on GHS/QoL
Inclusion Criteria
1) Participants assigned female at birth, 18 years of age or older (or minimum age according to country-specific requirements), and able to understand and give written informed consent.
2) Documented evidence of recurrent/persistent endometrial cancer (endometrial carcinoma or carcinosarcoma).
3) Up to 3 prior lines of systemic therapy for endometrial cancer, including systemic platinum-based chemotherapy and anti-PD-1/PD-L1 therapy, either in combination or separately.
• Neoadjuvant and/or adjuvant therapy is considered 1 prior line of systemic therapy.
• Prior monoclonal antibodies or targeted therapies, including but not limited to bevacizumab, poly (adenosine diphosphate-ribose) polymerase inhibitors, trastuzumab, will count as a line of treatment if given as a single agent with the intent of controlling disease. If these agents are given in combination with chemotherapy and continued as maintenance monotherapy, they will not be counted as a separate line of treatment.
• There is no restriction regarding prior hormonal or hormonal-based therapy. Hormonal or hormonal-based therapy does not count as a line of therapy.
• For participants who are ineligible for anti-PD-1/PD-L1 therapy due to medical comorbidities, or if anti-PD-1/PD-L1 agents are not available as standard-of-care therapy in any line of treatment according to local standards, prior treatment with an anti-PD-1/PD-L1 agent is not required.
4) Eligible for treatment with either doxorubicin or paclitaxel as determined by the investigator.
5) Radiologically evaluable disease (either measurable or nonmeasurable) by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria by investigator assessment (see Appendix 11.8).
• If a participant has disease based on pleural effusion or ascites alone (with no other radiologically evaluable lesions), this must be cytologically confirmed.
6) Documented disease progression by CT or MRI during or after the most recent therapy per RECIST v1.1 criteria by investigator assessment.
7) Availability of tumor tissue from an archival or fresh biopsy for assessment of Trop-2 and other study biomarkers. Tissue submission should be in the form of a formalin-fixed paraffin-embedded (FFPE) block (preferably) or ≥ 20 freshly sectioned, unstained slides. Tissue must be submitted within 4 weeks of randomization (for sites in China, see Appendix 11.10.1).
• If archival tumor tissue is available, it should preferably be from the most recently available tumor biopsy (obtained ideally within 12 months prior to randomization), from a locally recurrent or metastatic site. If archival tissue is not available, a fresh biopsy, preferably from a locally recurrent or metastatic site should be performed before randomization. Fine needle aspirates, bone biopsies, and cytology samples are not suitable samples. If < 20 unstained slides are available, and it is not clinically feasible to obtain a new biopsy, the participant may still be eligible upon consultation with the sponsor medical monitor.
8) Eastern Cooperative Oncology Group PS of 0 or 1 (see Appendix 11.7).
9) Meet the following organ function requirements: (See protocol)
10) Participants assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception (Section 11.5).
11) Life expectancy of ≥ 3 months.
12) Willing and able to comply with the requirements and restrictions in this protocol.
Exclusion Criteria
1) Uterine leiomyosarcoma and endometrial stromal sarcomas are excluded.
2) Participants who are candidates for curative-intent therapy at the time of study enrollment.
3) Participants eligible for rechallenge with platinum-based chemotherapy as determined by the investigator.
4) Received any prior treatment with a Trop-2-directed ADC.
5) Received any prior treatment (including an ADC) containing a chemotherapeutic agent targeting topoisomerase I.
6) Have had a prior anticancer biologic agent within 4 weeks prior to the first dose of study drug or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study drug.
7) Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drug.
8) Have not recovered (ie, Grade 2 or higher is considered not recovered) from AEs due to a previously administered agent.
• Participants with Grade 2 or lower neuropathy or any grade alopecia are an exception to this criterion and will qualify for the study.
• If participants underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Participants who underwent major surgery within 3 weeks of randomization are not eligible.
9) Need for ongoing systemic anticancer therapies aside from the study treatment.
10) Known or severe (Grade 3 or higher) hypersensitivity to SG and/or the chemotherapy regimen of choice in the TPC group (eg doxorubicin or paclitaxel), their metabolites, or formulation excipients.
11) Requirement for ongoing therapy with any prohibited medications listed in Section 5.6.2.
12) Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable CNS disease for ≥ 4 weeks prior to randomization and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking 10 mg/day or less of prednisone or its equivalent. All participants with carcinomatous meningitis are excluded regardless of clinical stability.
13) Have an active second malignancy.
• Participants with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to randomization, or participants with surgically cured tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll.
14) Left ventricular ejection fraction < 50% on screening echocardiogram or multigated acquisition (scan).
15) Have a history of significant cardiovascular disease, defined as:
• Myocardial infarction or unstable angina pectoris within 6 months of randomization.
• 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); history of QT interval prolongation.
• New York Heart Association Class III or greater congestive heart failure. 16) Have an active serious infection requiring systemic antimicrobial therapy.
17) Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody at screening) with detectable viral load OR taking medications that may interfere with SN-38 metabolism.
18) Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). 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 are excluded. Participants who test positive for hepatitis B core antibody will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease.
• Participants who test positive for HCV antibody will require HCV RNA by quantitative PCR for confirmation of active disease. Participants with a known history of HCV or a positive HCV antibody test will not require an HCV antibody at screening and will only require HCV RNA by quantitative PCR for confirmation of active disease.
19) Scheduled surgery during the study, other than a minor surgery that would not delay study treatment.
20) Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or gastrointestinal perforation within 6 months prior to randomization.
21) Have a positive serum pregnancy test (see Appendix 11.5) or are breastfeeding for participants who are assigned female at birth.
22) Use of any live vaccine against infectious diseases within 30 days of the first dose of study drug.
23) 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.
24) Any medical condition that, in the investigator’s or sponsor’s opinion, poses an undue risk to the participant’s participation in the study.
