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

Solid Tumors Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03965845
• Other study ID #: CX-839-012
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 25, 2019
• Est. completion date: September 24, 2021

Study information

• Verified date: September 2022
• Source: Calithera Biosciences, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: September 24, 2021
• Est. primary completion date: September 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• CRC
• KRAS Gene Mutation
• Neoplasms
• NSCLC
• Solid Tumors

Intervention

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.
• 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.

Locations

Country	Name	City	State
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	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	Sarah Cannon Research Institute- Tennessee Oncology	Nashville	Tennessee
United States	Regions Cancer care Center	Saint Paul	Minnesota
United States	South Texas Accelerated Research Therapeutic, LLC	San Antonio	Texas
United States	UCLA Hematology/Oncology	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Calithera Biosciences, Inc

Country where clinical trial is conducted

United States, 

Outcome

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