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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

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.