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

NCT03965845 | Completed Phase 1 FDA Drug

• 1 other identifier: CX-839-012
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 10

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability of telaglenestat (CB-839) in combination with palbociclib: (CR) number of participants with treatment related adverse events

  Number of participants with treatment related adverse events as assessed by CTCAE v5.0

  Start of treatment to 28 days post treatment

• Maximum tolerated dose and/or Recommended Phase 2 Dose:

  Incidence and nature of dose-limiting toxicities

  Measured from Part 1 patients only within their first 28 day cycle

Secondary Outcomes (2)

• Maximum plasma concentration of telaglenastat and palbociclib:

  PKs are drawn on two different days (Day 8 and Day 15) during Cycle 1

• Anti-tumor activity of telaglenestat and palbociclib:

  Approximately every 8 weeks until disease progression, for approximately 18 months

Study Arms (5)

Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg

EXPERIMENTAL

Drug: Telaglenestat (CB-839); Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mg

EXPERIMENTAL

Drug: Telaglenestat (CB-839); Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mg

EXPERIMENTAL

Drug: Telaglenestat (CB-839); Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mg

EXPERIMENTAL

Drug: Telaglenestat (CB-839); Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Part 2: Expansion

EXPERIMENTAL

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); Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Interventions

Telaglenestat (CB-839) 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.

Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg; Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mg; Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mg; Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mg; Part 2: Expansion

Palbociclib Oral Capsule or Tablet [Ibrance] 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.

Also known as: Ibrance

Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg; Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mg; Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mg; Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mg; Part 2: Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• small molecule TKI therapy (including investigational) within 2 weeks or 5 half-lives prior to expected Cycle 1 Day 1 dose
• any type of anti-cancer antibody or cytotoxic chemo within 4 weeks prior to Cycle 1 Day 1 Dose
• 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

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (10)

UCLA Hematology/Oncology

Santa Monica, California, 90095, United States

Location

Emory, Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Regions Cancer care Center

Saint Paul, Minnesota, 55101, United States

Location

Sarah Cannon Research Institute- Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutic, LLC

San Antonio, Texas, 78229, United States

Location

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

CB-839; palbociclib; Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Emil Kuriakose, MD

  Calithera Biosciences, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: May 29, 2019
• Study Start: June 25, 2019
• Primary Completion: September 24, 2021
• Study Completion: September 24, 2021
• Last Updated: September 19, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)