Safety and Efficacy Study in Adults With Advanced Solid Tumors Receiving REGN13089-M404-M2980, an Antibody-drug Conjugate That Targets MET Protein on Tumors

• REGN13089-M404-M2980 (Drug): Administered per the protocol

Primary outcomes

• Occurrence of dose-limiting toxicities (DLTs) [Up to 21 days]: Part 1 (Dose Escalation)
• Occurrence of Treatment Emergent Adverse Events (TEAEs) [Up to approximately 5 years]: Part 1 (Dose Escalation)
• Occurrence of Serious Adverse Events (SAEs) [Up to approximately 5 years]: Part 1 (Dose Escalation)
• Occurrence of adverse event of special interests (AESIs) [Up to approximately 5 years]: Part 1 (Dose Escalation)
• Objective response (OR) (investigator assessed) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 [Up to approximately 5 years]: Part 2 (Dose Expansion)

Secondary outcomes

• Objective response (investigator assessed) per RECIST 1.1 [Up to approximately 5 years]: Part 1 (Dose Escalation)
• Concentrations of ADC [Up to approximately 5 years]: Part 1 (Dose Escalation) and Part 2 (Dose Expansion)
• Concentrations of total antibody [Up to approximately 5 years]: Part 1 (Dose Escalation) and Part 2 (Dose Expansion)
• Concentrations of payload (ProDXd and DXd) [Up to approximately 5 years]: Part 1 (Dose Escalation) and Part 2 (Dose Expansion)
• Occurrence of Anti-Drug Antibodies (ADA) against REGN13089-M404-M2980 [Up to approximately 5 years]: Part 1 (Dose Escalation) and Part 2 (Dose Expansion)
• Magnitude of ADA against REGN13089-M404-M2980 [Up to approximately 5 years]: Part 1 (Dose Escalation) and Part 2 (Dose Expansion)
• Duration of response per RECIST 1.1 [Up to approximately 5 years]: Part 2 (Dose Expansion)
• Time to response per RECIST 1.1 [Up to approximately 5 years]: Part 2 (Dose Expansion)
• Progression-free survival per RECIST 1.1 [Up to approximately 5 years]: Part 2 (Dose Expansion)
• Overall survival [Up to approximately 5 years]: Part 2 (Dose Expansion)
• Occurrence of TEAEs considered clinically significant [Up to approximately 5 years]: Part 2 (Dose Expansion)
• Laboratory abnormalities considered clinically significant [Up to approximately 5 years]: Part 2 (Dose Expansion)

Sex: All, ages: 18 Years to any

Key Inclusion Criteria:

1. Histologically confirmed cancer (non-small cell lung cancer (epidermal growth factor receptor mutant type or epidermal growth factor receptor mutant type), colorectal cancer, gastric/gastroesophageal junction cancer, uveal melanoma, papillary renal cell carcinoma, or clear cell renal cell carcinoma) that is at an advanced stage as described in the protocol
2. Participants must not be candidates for curative surgery or radiation
3. Participants are required to have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease, or intolerance of the therapy as described in the protocol
4. Willing to provide tumor tissue; archival or fresh tumor tissue will be accepted as described in the protocol
5. At least 1 lesion that is measurable by RECIST 1.1. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions after radiation
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Adequate organ and bone marrow function as described in the protocol

Key Exclusion Criteria:

1. Has received treatment with an approved systemic therapy or has participated in any study of an investigational agent or investigational device as described in the protocol
2. Has received radiation therapy within the 28 days prior to first administration of study intervention. Palliative stereotactic radiation therapy without a thoracic or abdominal field is allowed with a washout period of 14 days from first administration of study intervention.
3. Has undergone major surgery within the 14 days prior to first administration of study intervention
4. Has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities resulting from prior therapy as described in the protocol
5. Has a history of interstitial lung disease (eg, idiopathic pulmonary fibrosis, etc) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management or has imaging consistent with these diseases during the screening period. A history of radiation pneumonitis is permitted as long as pneumonitis resolved ≥6 months prior to enrollment.
6. Has received prior treatment with an antibody-drug conjugate (ADC) that includes a topoisomerase payload
7. Known active or untreated brain metastases or spinal cord compression. Participants are eligible if central nervous system (CNS) metastases are adequately treated, and participants have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment.

Note: Other protocol defined inclusion/ exclusion criteria apply

• Clinical Trial Management, Study director, Regeneron Pharmaceuticals