PRO1184 for Advanced Solid Tumors

Open to people ages 18 years and up

• 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
• previously received therapies known to confer clinical benefit
• willing to provide a tumor sample (archive tissue or fresh biopsy)
• ECOG performance status 0 or 1
• measurable disease per RECIST v1.1 for all tumor types other than pleural mesothelioma which will use mRECIST v1.1 at baseline

• adequate hematologic, hepatic, renal and cardiac function

  Part C: High grade ovarian cancer:

• Patients must have platinum-resistant/refractory ovarian cancer
• Patients must have received prior bevacizumab
• Patients with known or suspected deleterious germline or somatic BRCA mutations must have been treated with a poly ADP-ribose polymerase (PARP) inhibitor
• 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
• 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 patient preference (and not disease progression) is not considered a separate line of therapy

  Part D: Cohort D1 (PRO1184+carboplatin):

• Patients must have platinum-sensitive ovarian cancer

• 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):

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

• other malignancy within 3 years
• active CNS metastases (treated, stable CNS metastases are allowed)
• uncontrolled Grade 3 or greater infection within 2 weeks
• positive for HBV, HCV or HIV
• use of a strong CYP3A inhibitor within 14 days (dose escalation only)
• prior therapy with a topoisomerase 1 inhibitor-based antibody drug conjugate
• additional protocol defined inclusion/exclusion criteria may apply