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

Calithera Biosciences

Status and phase: Terminated; Phase 2; Phase 1

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

Treatments: Drug: CB-839; Drug: Talazoparib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03875313

CX-839-011

Details and patient eligibility

About

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.

Enrollment: 33 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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33 participants in 5 patient groups

600 mg CB-839 + 1 mg Talazoparib

Experimental group

Description:

600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.

Treatment:

Drug: Talazoparib

Drug: CB-839

800 mg CB-839 + 1 mg Talazoparib: ccRCC

Experimental group

Description:

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.

Treatment:

Drug: Talazoparib

Drug: CB-839

800 mg CB-839 + 1 mg Talazoparib: TNBC

Experimental group

Description:

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.

Treatment:

Drug: Talazoparib

Drug: CB-839

800 mg CB-839 + 1 mg Talazoparib: CRC

Experimental group

Description:

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.

Treatment:

Drug: Talazoparib

Drug: CB-839

800 mg CB-839 + 1 mg Talazoparib: Other Histology

Experimental group

Description:

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).

Treatment:

Drug: Talazoparib

Drug: CB-839