Clinical trial NCT03875313: Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors
Official title: A Phase 1b/2 Open Label, Dose Escalation and Expansion Study of the Glutaminase Inhibitor CB-839 in Combination With the PARP Inhibitor Talazoparib in Patients With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Clear Cell Renal Cell Carcinoma
TNBC - Triple-Negative Breast Cancer
Colorectal Cancer
CRC
RCC
ccRCC
Keywords: Tumor Metabolism
Glutaminase Inhibitor
CB-839
telaglenastat
talazoparib
PARP Inhibitor
DNA Damage
DNA Repair
Homologous recombination deficiency
HRD
BRCA 1
BRCA 2
Lead sponsor: Calithera Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2019-03-14
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1b/2 study to determine the recommended phase 2 dose (RP2D), safety and tolerability, pharmacokinetics (PK) and clinical activity of the glutaminase inhibitor CB-839 with the poly adenosine diphosphate ribose polymerase (PARP) inhibitor talazoparib in participants with advanced/metastatic solid tumors.


Eligibility criteria: Inclusion Criteria:

(Part 1)

-Documented incurable/locally advanced or metastatic solid tumors that have either relapsed or are refractory or intolerant to standard therapies of proven clinical benefit.

(Part 2) Meets 1 of the 3 defined cohorts:

* Cohort 1: Documented incurable/locally advanced or metastatic ccRCC
* Cohort 2: Documented incurable/locally advanced or metastatic defined as ER, PR negative (\<1%) and HER2 negative (immunohistochemistry 0 to 1+ or fluorescence in situ hybridization \[FISH\] negative)
* Cohort 3: incurable/locally advanced or metastatic CRC

For both Parts 1 \& 2:

* Recovery to baseline or ≤ Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 from toxicities related to the prior therapy
* Adequate renal, hepatic, and hematological function
* Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 evaluable disease (Part 1) or measurable disease (Part 2)
* Ability to provide written consent in accordance with federal, local and institutional guidelines
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

Exclusion Criteria for both Parts 1 \& 2:

* Prior treatment with CB-839 or a PARP inhibitor
* Unable to received oral medications
* Active and/or untreated central nervous system metastasis. Patients with treated brain metastases must have (1) documented radiographic stability of at least 4 weeks duration demonstrated on baseline central nervous system (CNS) imaging prior to study treatment and (2) be symptomatically stable and off steroids for at least 2 weeks before administration of any study treatment.
* Major surgery within 28 days prior to first dose of study drug
* Receipt of any anticancer therapy within the following windows: small molecule tyrosine kinase inhibitor therapy (including investigational) within the prior 2 weeks or 5 half-lives prior to C1D1, whichever is longer; any type of anti-cancer antibody or cytotoxic chemotherapy within 4 weeks prior to C1D1; radiation therapy for bone metastasis within 2 weeks prior or any other external radiation therapy within 4 weeks prior to C1D1; patients with clinically relevant ongoing complications from prior radiation therapy are not eligible.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Excluding Deaths Due to Disease Progression
timeFrame: Start of treatment to 28 days post treatment; mean overall duration of talazoparib exposure was 88.7 days.
measure: Number of Participants With Laboratory Abnormalities (Hematology, Clinical Chemistry) at More Than 1 Clinic Visit
timeFrame: Hematology: screening, cycle 1 day 1, cycle 1 day 15, cycle 2 day 1, end of treatment (EOT). Clinical chemistry parameters: screening, cycle 1 day 1, cycle 1 day 8, cycle 1 day 15, cycle 1 day 22, cycle 2 day 1, cycle 2 day 15, EOT.
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: During Cycle 1 on Days 1 through 28, inclusive
measure: Overall Response Rate (ORR)
timeFrame: Maximum duration of follow-up for ORR was 12.9 months.
measure: Confirmed ORR (cORR)
timeFrame: Maximum duration of follow-up for cORR was 12.9 months.
measure: Clinical Benefit Rate (CBR)
timeFrame: Maximum duration of follow-up for CBR was 12.9 months.
measure: Progression-Free Survival (PFS)
timeFrame: Maximum duration of follow-up for PFS was 12.9 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Columbia University
state: New York
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Calithera Biosciences, Inc
name: Sam Whiting, MD, PhD
role: STUDY_DIRECTOR
References: