Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers

Phase Ib Study of Gevokizumab in Combination With Standard of Care Anti-cancer Therapies in Patients With Metastatic Colorectal Cancer, Gastroesophageal Cancer and Renal Cell Carcinoma

This study will determine the pharmacodynamically-active dose of gevokizumab and the tolerable dose of gevokizumab in combination with the standard of care anti-cancer therapy in patients with metastatic colorectal cancer, metastatic gastroesophageal cancer and metastatic renal cell carcinoma, and the preliminary efficacy of gevokizumab in combination with the SOC anti-cancer therapy in subjects with mCRC and mGEC.

Key Inclusion Criteria:

For All Cohorts:

• Adult ≥ 18 years old.
• Metastatic disease not amenable to potentially curative surgery and with available archival tumor tissue or fresh tumor tissue biopsy.
• Presence of at least 1 measurable lesion assessed by CT and/or MRI according to RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Adequate bone marrow and organ function per defined criteria in the protocol.
• Recovered from acute laboratory and clinical toxicities of prior anti cancer treatment to NCI CTCAE v5.0 grade ≤1 at time of screening, except alopecia and amenorrhea.

For Cohort A:

• First line metastatic colorectal adenocarcinoma.

For Cohort B:

• Second line metastatic colorectal adenocarcinoma that has progressed on prior line of chemotherapy administered for metastatic disease and which must include a fluoropyrimidine and oxaliplatin.

For Cohort C:

• Second line metastatic gastroesophageal adenocarcinoma that has progressed on prior line of chemotherapy administered for metastatic disease, and which must include a platinum agent and fluoropyrimidine doublet.

For Cohort D:

• Second or third line metastatic renal cell carcinoma with a clear cell component and has received one or two lines of treatment for metastatic disease that included an anti angiogenic agent for at least 4 weeks with radiologic progression on that treatment.

For subjects starting from Part 1a in Cohorts A and B:

• Serum hs CRP at screening ≥ 10 mg/L (per central laboratory assessment).
• Not requiring immediate initiation of anti cancer therapy per investigator's best judgement.

For subjects starting from Part 2 in Cohort C:

• Serum hs CRP at screening ≥ 10 mg/L (per central laboratory assessment).

Key Exclusion Criteria:

For All Cohorts:

• Currently receiving any of the prohibited medications or has contraindications as outlined in the 'Contraindications' to SOC regimen components.
• Symptomatic brain metastases or brain metastases that require directed therapy (such as focal radiotherapy or surgery).
• Suspected or proven immunocompromised state, or infections (as defined in the protocol).
• Conditions that have a high risk of clinically significant bleeding after administration of anti VEGF agents.
• Clinically significant, uncontrolled or recent (within last 6 months) cardiovascular disease.

For Cohort D:

• Concomitant medications, herbal supplements, and/or fruits and their juices that are known as strong inhibitors or inducers of CYP3A4/5, and medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
• Impairment of GI function or GI disease that may significantly alter the absorption of cabozantinib.

Other protocol-defined inclusion/exclusion criteria may apply