Clinical Trials /

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

NCT03965845

Description:

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 telaglenestat (CB-839) with the CDK4/6 Inhibitor, palbociclib in participants with advanced/metastatic solid tumors.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Telaglenastat (CB-839) in Combination With Palbociclib in Patients With Solid Tumors
  • Official Title: A Phase 1b/2, Open Label, Dose Escalation and Expansion Study of the Glutaminase Inhibitor Telaglenastat (CB-839) in Combination With CDK4/6 Inhibitor Palbociclib in Patients With Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CX-839-012
  • NCT ID: NCT03965845

Conditions

  • Solid Tumors
  • NSCLC
  • CRC
  • KRAS Gene Mutation

Interventions

DrugSynonymsArms
Telaglenestat (CB-839)Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg
Palbociclib Oral Capsule [Ibrance]IbranceCohort 1: Telaglenastat 600 mg and Palbociclib 75 mg

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 telaglenestat (CB-839) with the CDK4/6 Inhibitor, palbociclib in participants with advanced/metastatic solid tumors.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mgExperimental
  • Telaglenestat (CB-839)
  • Palbociclib Oral Capsule [Ibrance]
Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mgExperimental
  • Telaglenestat (CB-839)
  • Palbociclib Oral Capsule [Ibrance]
Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mgExperimental
  • Telaglenestat (CB-839)
  • Palbociclib Oral Capsule [Ibrance]
Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mgExperimental
  • Telaglenestat (CB-839)
  • Palbociclib Oral Capsule [Ibrance]
Part 2: ExpansionExperimentalThe recommended phase 2 dose (RP2D) determined from Part 1 will be the treatment for all cohorts in expansion Part 2.
  • Telaglenestat (CB-839)
  • Palbociclib Oral Capsule [Ibrance]

Eligibility Criteria

        Inclusion Criteria:

          -  Part 1: Have documented incurable/locally advanced or metastatic solid tumors that
             have either relapsed or are refractory or intolerant to the standard therapies of
             proven clinical benefit.

          -  Part 2: Availability of archival tumor tissue block or slides (Fresh tumor biopsy will
             be required if archival tissue is not available)

          -  Part 2, Cohort 1: Incurable/locally advanced or metastatic KRAS-mutant CRC previously
             treated with systemic therapy (examples include: oxaliplatin-, irinotecan-and 5
             FU-based chemotherapy (unless contraindicated) with or without bevacizumab)

          -  Part 2, Cohort 2: Incurable/locally advanced or metastatic KRAS-mutant NSCLC
             previously treated with systemic chemotherapy including platinum-based and
             anti-PD-1/PDL-1 therapy (unless contraindicated)

        For both Part 1 and 2:

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

          -  Ability to provide written consent in accordance with federal, local and institutional
             guidelines

          -  PER RECIST v1.1 evaluable disease (for part 1) or measurable disease (for Part 2)

          -  Recovery to baseline or to Grade 1 CTCAE v5.0 of toxicities that were related to prior
             therapies

        Exclusion Criteria:

          -  Prior treatment with CB-839 or palbociclib

          -  Unable to receive oral medication

          -  Infection requiring more than 5 days of parenteral antibiotics, antivirals, or
             antifungals within two weeks prior to C1D1

          -  Unable to discontinue proton pump inhibitor use before study treatment

          -  Refractory nausea and vomiting, uncontrolled diarrhea, malabsorption, significant
             small bowel resection or gastric bypass surgery, use of feeding tubes or other
             situation that may preclude adequate absorption

          -  Active and/or untreated central nervous system metastasis. Patients with treated brain
             metastasis must have (1) documented radiographic stability of at least 4 weeks in
             duration demonstrating on baseline central nervous system 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:

               1. small molecule TKI therapy (including investigational) within 2 weeks or 5
                  half-lives prior to expected Cycle 1 Day 1 dose

               2. any type of anti-cancer antibody or cytotoxic chemo within 4 weeks prior to Cycle
                  1 Day 1 Dose

               3. radiation therapy for bone metastasis within 2 weeks prior or any other external
                  radiation therapy within 4 weeks prior to C1D1

               4. patients with clinically relevant ongoing complications from prior radiation
                  therapy are not eligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and Tolerability of telaglenestat (CB-839) in combination with palbociclib: (CR) number of participants with treatment related adverse events
Time Frame:Start of treatment to 28 days post treatment
Safety Issue:
Description:Number of participants with treatment related adverse events as assessed by CTCAE v5.0

Secondary Outcome Measures

Measure:Maximum plasma concentration of telaglenastat and palbociclib:
Time Frame:PKs are drawn on two different days (Day 8 and Day 15) during Cycle 1
Safety Issue:
Description:Non-compartmental method of analysis will be used to analyze the plasma concentrations
Measure:Anti-tumor activity of telaglenestat and palbociclib:
Time Frame:Approximately every 8 weeks until disease progression, for approximately 18 months
Safety Issue:
Description:Change in tumor size from baseline

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Calithera Biosciences, Inc

Trial Keywords

  • Tumor Metabolism
  • Glutaminase Inhibitor
  • CB-839
  • Palbociclib
  • PALBO
  • Telaglenestat
  • CDK4/6
  • CDK4
  • CDK6

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