PRO1184 for Advanced Solid Tumors

Inclusion Criteria:

1. 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, breast cancer (hormone receptor positive, HER2-negative and triple-negative), mesothelioma
2. previously received therapies known to confer clinical benefit
3. willing to provide a tumor sample (archive tissue or fresh biopsy)
4. ECOG performance status 0 or 1
5. measurable disease per RECIST v1.1 for all tumor types other than pleural mesothelioma which will use mRECIST v1.1 at baseline
6. adequate hematologic, hepatic, renal and cardiac function

Part C:

High grade ovarian cancer:

1. Patients must have platinum-resistant/refractory ovarian cancer
2. Patients must have received prior bevacizumab
3. Patients with known or suspected deleterious germline or somatic BRCA mutations must have been treated with a poly ADP-ribose polymerase (PARP) inhibitor
4. Patients must have previously received mirvetuximab soravtansine, if indicated based on an FDA approved test for FRα expression (i.e., FRα PS2+ membrane expression in at least 75% of tumor cells), unless the patient has a documented medical exception
5. 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
6. A switch/change in regimen due solely to toxicity or patient preference (and not disease progression) is not considered a separate line of therapy

Part D:

Cohort D1 (PRO1184+carboplatin):

1. Patients must have platinum-sensitive ovarian cancer
2. Patients must have received 1 to 3 prior lines of therapy

Cohort D2 (PRO1184+bevacizumab):

-Patients must have platinum-resistant/refractory ovarian cancer

Cohort D3 (PRO1184+pembrolizumab):

1. Endometrial cancer (any subtype excluding sarcoma)
2. Patients must have received prior platinum-based chemotherapy for recurrent or advanced disease

Exclusion Criteria:

1. other malignancy within 3 years
2. active CNS metastases (treated, stable CNS metastases are allowed)
3. uncontrolled Grade 3 or greater infection within 2 weeks
4. positive for HBV, HCV or HIV
5. use of a strong CYP3A inhibitor within 14 days (dose escalation only)
6. prior therapy with a topoisomerase 1 inhibitor-based antibody drug conjugate

* additional protocol defined inclusion/exclusion criteria may apply