CANTATA: CB-839 With Cabozantinib vs. Cabozantinib With Placebo in Patients With Metastatic Renal Cell Carcinoma

Calithera Biosciences

Status and phase: Completed; Phase 2

Conditions: Metastatic Renal Cell Carcinoma; Advanced Renal Cell Carcinoma

Treatments: Drug: Placebo; Drug: Cabozantinib; Drug: CB-839

Study type: Interventional

Funder types: Industry

Identifiers

NCT03428217

CX-839-008

Details and patient eligibility

About

Tthe primary objective of this study is to compare blinded Independent Radiology Committee (IRC)-adjudicated progression free survival (PFS) of patients treated with CB-839 + cabozantinib (CB-Cabo) versus placebo + cabozantinib (Pbo-Cabo) for advanced or metastatic clear-cell RCC (ccRCC).

Enrollment: 444 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Documented histological or cytological diagnosis of renal cell carcinoma with a clear-cell component
2. Adult patients
3. Karnofsky Performance Score (KPS) ≥ 70%
4. Measurable Disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
5. 1-2 lines of prior therapy for advanced or metastatic renal cell carcinoma (RCC) including one anti-angiogenic therapy (any vascular endothelial growth factor [VEGF] pathway-targeted agent used either as monotherapy or as a component of a combination regimen) OR the combination regimen of nivolumab + ipilimumab
6. Adequate hepatic, renal, cardiac and hematologic function

Exclusion criteria

1. Prior treatment with cabozantinib (or other mesenchymal-epithelial transition [MET] inhibitor) or CB-839
2. Receipt of other anticancer therapy within 2-6 weeks, depending on the treatment
3. Untreated or active brain metastases or central nervous system cancer, as defined per protocol
4. Prior gastric surgery, small bowel resection, or other conditions that may impede adequate absorption of oral study drug
5. Known active infection with human immunodeficiency virus (HIV), Hepatitis B or C virus
6. Inability to discontinue proton-pump-inhibitor use before randomization
7. Patients who are pregnant or lactating

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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444 participants in 2 patient groups, including a placebo group

Pbo-Cabo

Placebo Comparator group

Description:

Placebo twice daily (BID) + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.

Treatment:

Drug: Cabozantinib

Drug: Placebo

CB-Cabo

Experimental group

Description:

CB-839 800 mg BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.

Treatment:

Drug: CB-839

Drug: Cabozantinib