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

Phase 1

Completed

• Conditions: NSCLC; Solid Tumors; CRC; KRAS Gene Mutation
• Interventions: Drug: Telaglenestat (CB-839); Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

• Registration Number: NCT03965845
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-05-24
• Study First Submitted QC: 2019-05-24
• Study First Posted: 2019-05-29
• Study Start: 2019-06-25
• Primary Completion: 2021-09-24
• Study Completion: 2021-09-24
• Status Verified: 2022-09
• Disposition First Submitted: 2022-09-14
• Disposition First Submitted QC: 2022-09-14
• Last Update Submitted: 2022-09-14
• Disposition First Posted: 2022-09-19
• Last Update Posted: 2022-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mg	Palbociclib Oral Capsule or Tablet [Ibrance]	-
Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mg	Palbociclib Oral Capsule or Tablet [Ibrance]	-
Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mg	Telaglenestat (CB-839)	-
Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mg	Palbociclib Oral Capsule or Tablet [Ibrance]	-
Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg	Telaglenestat (CB-839)	-
Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mg	Telaglenestat (CB-839)	-
Part 2: Expansion	Telaglenestat (CB-839)	The recommended phase 2 dose (RP2D) determined from Part 1 will be the treatment for all cohorts in expansion Part 2.
Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg	Palbociclib Oral Capsule or Tablet [Ibrance]	-
Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mg	Telaglenestat (CB-839)	-
Part 2: Expansion	Palbociclib Oral Capsule or Tablet [Ibrance]	The recommended phase 2 dose (RP2D) determined from Part 1 will be the treatment for all cohorts in expansion Part 2.

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability of telaglenestat (CB-839) in combination with palbociclib: (CR) number of participants with treatment related adverse events	Start of treatment to 28 days post treatment	Number of participants with treatment related adverse events as assessed by CTCAE v5.0
Maximum tolerated dose and/or Recommended Phase 2 Dose:	Measured from Part 1 patients only within their first 28 day cycle	Incidence and nature of dose-limiting toxicities

Secondary Outcome Measures

Name	Time	Method
Maximum plasma concentration of telaglenastat and palbociclib:	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
Anti-tumor activity of telaglenestat and palbociclib:	Approximately every 8 weeks until disease progression, for approximately 18 months	Change in tumor size from baseline

Trial Locations

Locations (10)

Emory, Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Regions Cancer care Center; 🇺🇸 Saint Paul, Minnesota, United States

MD Anderson; 🇺🇸 Houston, Texas, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

University of Wisconsin Clinical Science Center; 🇺🇸 Madison, Wisconsin, United States

UCLA Hematology/Oncology; 🇺🇸 Santa Monica, California, United States

Sarah Cannon Research Institute- Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

South Texas Accelerated Research Therapeutic, LLC; 🇺🇸 San Antonio, Texas, United States

Northwestern University Feinberg School of Medicine; 🇺🇸 Chicago, Illinois, United States