Clinical trial NCT03965845: A Study of Telaglenastat (CB-839) in Combination With Palbociclib in Patients With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
NSCLC
CRC
KRAS Gene Mutation
Keywords: Tumor Metabolism
Glutaminase Inhibitor
CB-839
Palbociclib
PALBO
Telaglenestat
CDK4/6
CDK4
CDK6
Lead sponsor: Calithera Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2019-05-29
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety and Tolerability of telaglenestat (CB-839) in combination with palbociclib: (CR) number of participants with treatment related adverse events
timeFrame: Start of treatment to 28 days post treatment
measure: Maximum tolerated dose and/or Recommended Phase 2 Dose:
timeFrame: Measured from Part 1 patients only within their first 28 day cycle
Secondary outcomes:
measure: Maximum plasma concentration of telaglenastat and palbociclib:
timeFrame: PKs are drawn on two different days (Day 8 and Day 15) during Cycle 1
measure: Anti-tumor activity of telaglenestat and palbociclib:
timeFrame: Approximately every 8 weeks until disease progression, for approximately 18 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Atlanta
country: United States
facility: Emory, Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Saint Paul
country: United States
facility: Regions Cancer care Center
state: Minnesota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute- Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutic, LLC
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Clinical Science Center
state: Wisconsin
Study officials:
affiliation: Calithera Biosciences, Inc
name: Emil Kuriakose, MD
role: STUDY_DIRECTOR
References: