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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03965845
Recruitment Status : Recruiting
First Posted : May 29, 2019
Last Update Posted : November 6, 2019
Sponsor:
Information provided by (Responsible Party):
Calithera Biosciences, Inc

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

Condition or disease Intervention/treatment Phase
Solid Tumors NSCLC CRC KRAS Gene Mutation Drug: Telaglenestat (CB-839) Drug: Palbociclib Oral Capsule [Ibrance] Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 25, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Palbociclib

Arm Intervention/treatment
Experimental: Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg Drug: Telaglenestat (CB-839)
Teleglenastat is an oral tablet administered twice daily with food at the assigned dose level. Dose is taken with palbociclib each day in 28-day cycles.

Drug: Palbociclib Oral Capsule [Ibrance]
Palbociclib (Ibrance) is an oral capsule administered once daily with food on Days 1-21 of every 28-day cycle in combination with telaglenestat. Days 22-28 of every cycle, palbociclib is not taken.
Other Name: Ibrance

Experimental: Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mg Drug: Telaglenestat (CB-839)
Teleglenastat is an oral tablet administered twice daily with food at the assigned dose level. Dose is taken with palbociclib each day in 28-day cycles.

Drug: Palbociclib Oral Capsule [Ibrance]
Palbociclib (Ibrance) is an oral capsule administered once daily with food on Days 1-21 of every 28-day cycle in combination with telaglenestat. Days 22-28 of every cycle, palbociclib is not taken.
Other Name: Ibrance

Experimental: Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mg Drug: Telaglenestat (CB-839)
Teleglenastat is an oral tablet administered twice daily with food at the assigned dose level. Dose is taken with palbociclib each day in 28-day cycles.

Drug: Palbociclib Oral Capsule [Ibrance]
Palbociclib (Ibrance) is an oral capsule administered once daily with food on Days 1-21 of every 28-day cycle in combination with telaglenestat. Days 22-28 of every cycle, palbociclib is not taken.
Other Name: Ibrance

Experimental: Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mg Drug: Telaglenestat (CB-839)
Teleglenastat is an oral tablet administered twice daily with food at the assigned dose level. Dose is taken with palbociclib each day in 28-day cycles.

Drug: Palbociclib Oral Capsule [Ibrance]
Palbociclib (Ibrance) is an oral capsule administered once daily with food on Days 1-21 of every 28-day cycle in combination with telaglenestat. Days 22-28 of every cycle, palbociclib is not taken.
Other Name: Ibrance

Experimental: Part 2: Expansion
The recommended phase 2 dose (RP2D) determined from Part 1 will be the treatment for all cohorts in expansion Part 2.
Drug: Telaglenestat (CB-839)
Teleglenastat is an oral tablet administered twice daily with food at the assigned dose level. Dose is taken with palbociclib each day in 28-day cycles.

Drug: Palbociclib Oral Capsule [Ibrance]
Palbociclib (Ibrance) is an oral capsule administered once daily with food on Days 1-21 of every 28-day cycle in combination with telaglenestat. Days 22-28 of every cycle, palbociclib is not taken.
Other Name: Ibrance




Primary Outcome Measures :
  1. 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 ]
    Number of participants with treatment related adverse events as assessed by CTCAE v5.0

  2. Maximum tolerated dose and/or Recommended Phase 2 Dose: [ Time Frame: Measured from Part 1 patients only within their first 28 day cycle ]
    Incidence and nature of dose-limiting toxicities


Secondary Outcome Measures :
  1. Maximum plasma concentration of telaglenastat and palbociclib: [ Time Frame: PKs are drawn on two different days (Day 8 and Day 15) during Cycle 1 ]
    Non-compartmental method of analysis will be used to analyze the plasma concentrations

  2. Anti-tumor activity of telaglenestat and palbociclib: [ Time Frame: Approximately every 8 weeks until disease progression, for approximately 18 months ]
    Change in tumor size from baseline



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03965845


Contacts
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Contact: Clinical Administrator 650-870-1000 clinicaltrials@calithera.com

Locations
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United States, Georgia
Emory, Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Olatunji Alese, MD    404-778-1900    olatunji.alese@emory.edu   
Principal Investigator: Olatunji Alese, MD         
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Amanda Eckert    713-745-8074    ACEckert@mdanderson.org   
Principal Investigator: Funda Meric Bernstam, MD         
South Texas Accelerated Research Therapeutic, LLC Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez    210-593-5265    isabel.jimenez@startsa.com   
Principal Investigator: Kyriakos Papadopoulos, MD         
Sponsors and Collaborators
Calithera Biosciences, Inc
Investigators
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Study Director: Sam Whiting, MD, PhD Calithera Biosciences, Inc
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Responsible Party: Calithera Biosciences, Inc
ClinicalTrials.gov Identifier: NCT03965845    
Other Study ID Numbers: CX-839-012
First Posted: May 29, 2019    Key Record Dates
Last Update Posted: November 6, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Calithera Biosciences, Inc:
Tumor Metabolism
Glutaminase Inhibitor
CB-839
Palbociclib
PALBO
Telaglenestat
CDK4/6
CDK4
CDK6
Additional relevant MeSH terms:
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Neoplasms
Palbociclib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action