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

Novartis

Status and phase: Active, not recruiting; Phase 1

Conditions: Gastroesophageal Cancer; Renal Cell Carcinoma; Colorectal Cancer

Treatments: Drug: Cabozantinib; Drug: FOLFIRI; Drug: Gevokizumab; Drug: Ramucirumab; Drug: Bevacizumab; Drug: Paclitaxel; Drug: Modified FOLFOX6

Study type: Interventional

Funder types: Industry

Identifiers

NCT03798626

CVPM087A2101

2018-003952-19 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 167 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

For Cohort A:

• First line metastatic colorectal cancer.

For Cohort B:

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

For Cohort C:

• Second line metastatic gastroesophageal cancer 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.
• 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.

Exclusion criteria

For All Cohorts:

• Currently receiving any of the prohibited medications or has contraindications as outlined in the protocol.
• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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167 participants in 4 patient groups

Cohort A: 1st line colorectal cancer

Experimental group

Description:

Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab

Treatment:

Drug: Modified FOLFOX6

Drug: Bevacizumab

Drug: Gevokizumab

Cohort B: 2nd line colorectal cancer

Experimental group

Description:

Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab

Treatment:

Drug: Bevacizumab

Drug: Gevokizumab

Drug: FOLFIRI

Cohort C: 2nd line gastroesophageal cancer

Experimental group

Description:

Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab

Treatment:

Drug: Paclitaxel

Drug: Ramucirumab

Drug: Gevokizumab

Cohort D: 2nd or 3rd line renal cell carcinoma

Experimental group

Description:

Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib

Treatment:

Drug: Gevokizumab

Drug: Cabozantinib