A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Comparing CB-839 in Combination With Everolimus (CBE) vs. Placebo With Everolimus (PboE) in Patients With Advanced or Metastatic Renal Cell Carcinoma (RCC)
Overview
- Phase
- Phase 2
- Intervention
- CB-839
- Conditions
- Clear Cell Renal Cell Carcinoma
- Sponsor
- Calithera Biosciences, Inc
- Enrollment
- 69
- Locations
- 38
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The primary objective of this study is to compare the progression-free survival (PFS) of participants treated with telaglenastat and everolimus versus placebo and everolimus for advanced or metastatic clear cell renal cell carcinoma (ccRCC) previously treated with the following:
- At least 2 lines of therapy, including at least 1 vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI)
- Radiographic progression of metastatic RCC must have occurred (per investigator assessment) on or after the most recent systemic therapy and within 6 months prior to cycle 1 day 1
Investigators
Eligibility Criteria
Inclusion Criteria
- •Karnofsky Performance Score (KPS) ≥ 70%
- •Estimated Life Expectancy of at least 3 months
- •Documented histological or cytological diagnosis of renal cell carcinoma with a clear-cell component.
- •Measurable Disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the Investigator
- •Must have received at least two prior lines of systemic therapy, including at least one VEGF TKI (e.g., sunitinib, sorafenib, pazopanib, cabozantinib)
- •a) Radiographic progression of mRCC must have occurred (per investigator assessment) on or after the most recent systemic therapy and within 6 months prior to Cycle 1 Day 1 (C1D1).
- •Prior treatment with other anti-cancer therapies including cytokines, monoclonal antibodies, immunotherapies, and cytotoxic chemotherapy is allowed
Exclusion Criteria
- •Prior treatment with mammalian target of rapamycin (mTOR) inhibitors (everolimus or temsirolimus) or CB-839
- •Receipt of any anticancer therapy within the following windows before randomization:
- •TKI therapy within 2 weeks or 5 half-lives, whichever is longer
- •Any type of anti-cancer antibody within 4 weeks
- •Cytotoxic chemotherapy within 4 weeks
- •Investigational therapy within 4 weeks or 5 half-lives, whichever is longer
- •Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization. Patients with clinically relevant ongoing complications from prior radiation therapy are not eligible.
- •Unable to receive medications orally (PO) or any condition that may prevent adequate absorption of oral study medication
- •Major surgery within 28 days prior to randomization
- •Patients with active and/or untreated central nervous system (CNS) cancer are not eligible. Patients with treated brain metastasis must have 1) documented radiographic stability of at least 4 weeks duration demonstrated on baseline contrast-enhanced CNS imaging (eg contrast-enhanced magnetic resonance imaging \[MRI\] of the brain) prior to randomization and 2) must be symptomatically stable and off steroids for at least 2 weeks before randomization.
Arms & Interventions
CB-839 + Everolimus
CB-839 is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles.
Intervention: CB-839
CB-839 + Everolimus
CB-839 is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles.
Intervention: everolimus
Placebo + Everolimus
Placebo is administered as oral tablets BID in combination with standard QD everolimus in 28 day cycles.
Intervention: Placebo
Placebo + Everolimus
Placebo is administered as oral tablets BID in combination with standard QD everolimus in 28 day cycles.
Intervention: everolimus
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: As of the primary data cutoff date of 26 Apr 2019; maximum duration of follow-up for PFS was 11.2 months.
PFS was defined as the time from randomization to the date of documented disease progression (assessed by Investigator per Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1) within 2 scheduled scan intervals following previous evaluable radiologic tumor assessment or death for any cause, whichever occurred first. Participants with no documentation of disease progression or death on-study were censored at the date of last available tumor assessment. Progressive Disease (PD) per RECIST 1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.
Secondary Outcomes
- Overall Survival (OS)(As of the data cutoff date of 30 Sep 2020; maximum duration of follow-up for OS was 30.4 months.)