Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)

Part A and B:

• Histologically or cytologically confirmed metastatic or unresectable solid malignancy including ovarian cancer (must have epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer), endometrial cancer, non-small cell lung cancer (Part A), EGFR-mutated NSCLC (Part B), breast cancer (hormone receptor positive, HER2-negative and triple-negative) (Part A), mesothelioma.
• Previously received therapies known to confer clinical benefit.
• Measurable disease per RECIST v1.1 for all tumor types other than pleural mesothelioma which will use mRECIST v1.1 at baseline. Part C: Participants must have histologically or cytologically confirmed metastatic or unresectable epithelial ovarian cancer as specified below.
• High grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (excluding endometrioid, clear cell carcinomas, mucinous, low grade, and those with a sarcomatous or neuroendocrine element)
• Participants must have received 1 to 3 prior lines of therapy. Participants who had 1 to 4 prior lines of therapy are allowed if mirvetuximab soravtansine (MIRV) was the last line of therapy. Participants must have progressed radiographically on or after their most recent line of therapy.
• Participants must have platinum-resistant ovarian cancer.
• Participants must have received prior bevacizumab.
• Participants with known or suspected deleterious germline or somatic BRCA mutations (as determined by Food and Drug Administration [FDA]-approved test in a Clinical Laboratory Improvement Amendments [CLIA]-certified laboratory) and who achieved a complete or partial response to platinum-based chemotherapy must have been treated with a poly ADP-ribose polymerase (PARP) inhibitor as maintenance treatment.
• Participants must have known FRα status based on an FDA approved test. Those who are FRα positive must have previously received MIRV, unless the participant has a documented medical exception.
• Participants who are FRα negative, in accordance with the FDA approved test (Ventana folate receptor [FOLR1] RxDx Assay), and were treated with MIRV, are excluded.
• Measurable disease per the RECIST v1.1 at baseline. Part D: Cohort D1 (Rina-S+carboplatin):
• Participants must have platinum-sensitive ovarian cancer.
• Participants must have received 1 to 3 prior lines of therapy. Cohort D2 (Rina-S+bevacizumab):
• Participants must have primary platinum-refractory, platinum-resistant, or platinum-sensitive ovarian cancer.
• Participants with primary platinum-refractory ovarian cancer must have received ≤2 prior lines of therapy. Primary platinum-refractory ovarian cancer is defined as a lack of response or by progression within 91 days after completing front-line platinum containing therapy.
• Participants must have received 1 to 3 prior lines of therapy for platinum-resistant ovarian cancer (PROC), and up to 4 prior lines of therapy for platinum-sensitive ovarian cancer (PSOC). Prior treatments may have included bevacizumab, PARP inhibitor, and MIRV.
  • Participants with PSOC must have disease progression on or after maintenance treatment, or at least 6 months (>183 days) or more from the last dose of platinum-based therapy. Cohort D3 (Rina-S+pembrolizumab):
• Endometrial cancer (any subtype excluding sarcoma).
• Participants must have received prior platinum-based chemotherapy for recurrent or advanced disease. Part F:
• Participants must have histologically or cytologically confirmed endometrial cancer as specified below.
• Advanced, recurrent, metastatic, or primary unresectable endometrial cancer (any subtype excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma)
• Participants must have received 1 to 3 prior lines of therapy in advanced, recurrent, or metastatic setting, and must have progressed radiographically on or after their most recent line of therapy:
• Participants must have received prior platinum-based chemotherapy and a programmed death-ligand 1 (PD-[L])1 inhibitor.
• Participants who progress >12 months after completion of prior adjuvant or neoadjuvant platinum-based chemotherapy must receive 1 additional cytotoxic systemic treatment prior to enrollment in this study.
• Hormonal therapy alone (i.e., without chemotherapy) will not be counted as a separate line of therapy.
• Measurable disease per the RECIST Version 1.1 at baseline.

• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids within the past 2 years, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Use of a strong cytochrome P450 3A (CYP3A) inhibitor within 14 days (dose escalation only).
• Prior therapy with a topoisomerase 1 inhibitor-based antibody drug conjugate. Note: Other protocol-defined inclusion/exclusion may apply.