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

NCT ID: NCT03965845

Last Updated: 2022-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-25
• Study Completion Date: 2021-09-24

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.

Conditions

Solid Tumors; NSCLC; CRC; KRAS Gene Mutation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg

Group Type: EXPERIMENTAL

Telaglenestat (CB-839)

Intervention Type: DRUG

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.

Palbociclib Oral Capsule or Tablet [Ibrance]

Intervention Type: DRUG

Palbociclib (Ibrance) is an oral capsule or tablet 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.

Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mg

Group Type: EXPERIMENTAL

Telaglenestat (CB-839)

Intervention Type: DRUG

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.

Palbociclib Oral Capsule or Tablet [Ibrance]

Intervention Type: DRUG

Palbociclib (Ibrance) is an oral capsule or tablet 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.

Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mg

Group Type: EXPERIMENTAL

Telaglenestat (CB-839)

Intervention Type: DRUG

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.

Palbociclib Oral Capsule or Tablet [Ibrance]

Intervention Type: DRUG

Palbociclib (Ibrance) is an oral capsule or tablet 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.

Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mg

Group Type: EXPERIMENTAL

Telaglenestat (CB-839)

Intervention Type: DRUG

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.

Palbociclib Oral Capsule or Tablet [Ibrance]

Intervention Type: DRUG

Palbociclib (Ibrance) is an oral capsule or tablet 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.

Part 2: Expansion

The recommended phase 2 dose (RP2D) determined from Part 1 will be the treatment for all cohorts in expansion Part 2.

Group Type: EXPERIMENTAL

Telaglenestat (CB-839)

Intervention Type: DRUG

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.

Palbociclib Oral Capsule or Tablet [Ibrance]

Intervention Type: DRUG

Palbociclib (Ibrance) is an oral capsule or tablet 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.

Interventions

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.

Intervention Type: DRUG

Palbociclib Oral Capsule or Tablet [Ibrance]

Palbociclib (Ibrance) is an oral capsule or tablet 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.

Intervention Type: DRUG

Other Intervention Names

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)
• Part 2, Cohort 3: Advance KRAS-mutant Pancreatic Ductal Adenocarcinoma (PDAC) harboring a mutation or loss in CDKN2A (PDAC) and received treatment with one or more lines of systemic chemotherapy with FOLFIRINOX and/or gemcitabine/abraxane in the neoadjuvant, adjuvant, or metastatic disease setting or unable to receive standard of care chemotherapy

Cohort 4 may be opened only if Cohort 3 achieves predefined criteria for efficacy

-Part 2 Cohort 4: Advanced KRAS-mutant Pancreatic Ductal Adenocarcinoma (PDAC). · Histological or cytological diagnosis of advanced or metastatic KRAS-mutant with CDKN2A wild type (PDAC) and received treatment with one or more lines of systemic chemotherapy with FOLFIRINOX and/or gemcitabine/abraxane in the neoadjuvant, adjuvant, or metastatic disease setting or unable to receive standard of care chemotherapy.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Calithera Biosciences, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emil Kuriakose, MD

Role: STUDY_DIRECTOR

Calithera Biosciences, Inc

Locations

UCLA Hematology/Oncology

Santa Monica, California, United States

Emory, Winship Cancer Institute

Atlanta, Georgia, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Regions Cancer care Center

Saint Paul, Minnesota, United States

Sarah Cannon Research Institute- Tennessee Oncology

Nashville, Tennessee, United States

MD Anderson

Houston, Texas, United States

South Texas Accelerated Research Therapeutic, LLC

San Antonio, Texas, United States

University of Wisconsin Clinical Science Center

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

CX-839-012

Identifier Type: -

Identifier Source: org_study_id