CRC, KRAS Gene Mutation, NSCLC, Solid Tumors
Conditions
Keywords
Tumor Metabolism, Glutaminase Inhibitor, CB-839, Palbociclib, PALBO, Telaglenestat, CDK4/6, CDK4, CDK6
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.
Interventions
DRUGTelaglenestat (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.
DRUGPalbociclib 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.
Sponsors
Calithera Biosciences, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed