Mass General - Division of Clinical Research

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 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. - Prior induction plus maintenance is considered 1 line of therapy, even if parts of the treatment regimen (induction or maintenance) are interrupted and/or resumed at a later date, in the absence of disease progression while on active treatment. - A switch/change in regimen due solely to toxicity or participant preference (and not disease progression) is not considered a separate line of therapy. 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 platinum-refractory, platinum-resistant, or platinum-sensitive ovarian cancer. - 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. Cohort D3 (Rina-S+pembrolizumab): - Endometrial cancer (any subtype excluding sarcoma). - Participants must have received prior platinum-based chemotherapy for recurrent or advanced disease.

• 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.