Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors

Purpose

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.

Conditions

  • Solid Tumor
  • Clear Cell Renal Cell Carcinoma
  • TNBC - Triple-Negative Breast Cancer
  • Colorectal Cancer
  • CRC
  • RCC
  • ccRCC

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
600 mg CB-839 + 1 mg Talazoparib 		600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.
  • Drug: CB-839
    CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.
    Other names:
    • telaglenastat
  • Drug: Talazoparib
    Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.
    Other names:
    • Talzenna
Experimental
800 mg CB-839 + 1 mg Talazoparib: ccRCC 		800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received ≥ 2 prior systemic regimens including ≥ 1 vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) therapy.
  • Drug: CB-839
    CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.
    Other names:
    • telaglenastat
  • Drug: Talazoparib
    Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.
    Other names:
    • Talzenna
Experimental
800 mg CB-839 + 1 mg Talazoparib: TNBC 		800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic triple-negative breast cancer (TNBC) estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior poly adenosine diphosphate ribose polymerase (PARP) inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.
  • Drug: CB-839
    CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.
    Other names:
    • telaglenastat
  • Drug: Talazoparib
    Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.
    Other names:
    • Talzenna
Experimental
800 mg CB-839 + 1 mg Talazoparib: CRC 		800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic colorectal cancer (CRC) who received appropriate oxaliplatin or irinotecan- and fluorouracil (5-FU)-based chemotherapy with or without bevacizumab.
  • Drug: CB-839
    CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.
    Other names:
    • telaglenastat
  • Drug: Talazoparib
    Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.
    Other names:
    • Talzenna
Experimental
800 mg CB-839 + 1 mg Talazoparib: Other Histology 		800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).
  • Drug: CB-839
    CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.
    Other names:
    • telaglenastat
  • Drug: Talazoparib
    Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.
    Other names:
    • Talzenna

More Details

Status
Terminated
Sponsor
Calithera Biosciences, Inc

Study Contact