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

Sponsor

Calithera Biosciences, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT03965845

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

5.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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 or Tablet [Ibrance]	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

53 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 :

Jun 25, 2019

Actual Primary Completion Date :

Sep 24, 2021

Actual Study Completion Date :

Sep 24, 2021

Arms and Interventions

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 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. Other Names: 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 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. Other Names: 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 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. Other Names: 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 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. Other Names: 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 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. Other Names: Ibrance

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Hematology/Oncology	Santa Monica	California	United States	90095
2	Emory, Winship Cancer Institute	Atlanta	Georgia	United States	30322
3	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
4	Rush University Medical Center	Chicago	Illinois	United States	60612
5	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
6	Regions Cancer care Center	Saint Paul	Minnesota	United States	55101
7	Sarah Cannon Research Institute- Tennessee Oncology	Nashville	Tennessee	United States	37203
8	MD Anderson	Houston	Texas	United States	77030
9	South Texas Accelerated Research Therapeutic, LLC	San Antonio	Texas	United States	78229
10	University of Wisconsin Clinical Science Center	Madison	Wisconsin	United States	53792