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

• ClinicalTrials.gov Identifier: NCT03428217
• Recruitment Status: Completed
• First Posted: February 9, 2018
• Last Update Posted: August 23, 2021
• Sponsor: Calithera Biosciences, Inc
• Information provided by (Responsible Party): Calithera Biosciences, Inc

Tracking Information

• First Submitted Date: February 5, 2018
• First Posted Date: February 9, 2018
• Last Update Posted Date: August 23, 2021
• Actual Study Start Date: May 14, 2018
• Actual Primary Completion Date: August 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 20, 2019)

Progression Free Survival (PFS) [ Time Frame: 18 months ]

An independent adjudication of radiological assessments will be conducted by Independent Radiology Committee (IRC) reviewing PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Original Primary Outcome Measures (submitted: February 5, 2018)

Progression Free Survival (PFS) [ Time Frame: 18 months ]

Assessed by Independent Radiology Committee (IRC)-adjudicated PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Current Secondary Outcome Measures (submitted: February 5, 2018)

• Overall Survival (OS) of study patients treated with CB-Cabo vs Pbo-Cabo [ Time Frame: 36 months ]
  Assessed by time from randomization to death by any cause
• PFS of patients treated with CB-Cabo vs Pbo-Cabo [ Time Frame: 18 months ]
  Assessed by investigator per RECIST v1.1

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CANTATA: CB-839 With Cabozantinib vs. Cabozantinib With Placebo in Patients With Metastatic Renal Cell Carcinoma
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial Comparing CB-839 in Combination With Cabozantinib (CB-Cabo) vs. Placebo With Cabozantinib (Pbo-Cabo) in Patients With Advanced or Metastatic Renal Cell Carcinoma (RCC)
• Brief Summary: This clinical trial is a randomized Phase 2 evaluation of CB-839 (telaglenastat) in combination with cabozantinib versus placebo with cabozantinib in patients with advanced or metastatic Renal Cell Carcinoma with a clear cell component.
• Detailed Description: This clinical trial is a randomized Phase 2 evaluation of CB-839 (telaglenastat) in combination with cabozantinib versus placebo with cabozantinib in Renal Cell Carcinoma patients with at least one and not more than 2 prior therapies in the advanced or metastatic setting.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a double blinded placebo-controlled study where patients will be randomized 1:1 to either CB-839 (telaglenastat) plus cabozantinib or placebo plus cabozantinib

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Participants, care providers, investigators and outcomes assessors are blinded to treatment. Progression free survival (PFS) will be assessed by a blinded Independent Radiology Committee for the primary endpoint of the study.

Primary Purpose: Treatment

Condition

• Advanced Renal Cell Carcinoma
• Metastatic Renal Cell Carcinoma

Intervention

• Drug: CB-839
  Oral glutaminase inhibitor
  Other Name: telaglenastat
• Drug: Cabozantinib
  Oral receptor tyrosine kinase inhibitor
  Other Names:

  • Cabometyx
  • Cabometriq
• Drug: Placebo
  Placebo tablets

Study Arms

• Experimental: CB-Cabo
  CB-839 orally twice daily + cabozantinib orally once daily
  Interventions:

  • Drug: CB-839
  • Drug: Cabozantinib
• Placebo Comparator: Pbo-Cabo
  Placebo orally twice daily + cabozantinib orally once daily
  Interventions:

  • Drug: Cabozantinib
  • Drug: Placebo

• Publications *: Tannir NM, Agarwal N, Porta C, Lawrence NJ, Motzer R, McGregor B, Lee RJ, Jain RK, Davis N, Appleman LJ, Goodman O Jr, Stadler WM, Gandhi S, Geynisman DM, Iacovelli R, Mellado B, Sepulveda Sanchez JM, Figlin R, Powles T, Akella L, Orford K, Escudier B. Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial. JAMA Oncol. 2022 Oct 1;8(10):1411-1418. doi: 10.1001/jamaoncol.2022.3511.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 11, 2019): 445
• Original Estimated Enrollment (submitted: February 5, 2018): 298
• Actual Study Completion Date: July 16, 2021
• Actual Primary Completion Date: August 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 RECIST 1.1
5. 1-2 lines of prior therapy for advanced or metastatic RCC including one anti-angiogenic therapy (any 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 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 HIV, Hepatitis B or C virus
6. Inability to discontinue proton-pump-inhibitor use before randomization
7. Patients who are pregnant or lactating

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Germany, Italy, New Zealand, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03428217
• Other Study ID Numbers: CX-839-008
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Calithera Biosciences, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Calithera Biosciences, Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Sam Whiting, M.D., Ph.D.; Calithera Biosciences, Inc

• PRS Account: Calithera Biosciences, Inc
• Verification Date: August 2021