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

Calithera Biosciences

Status and phase: Completed; Phase 2; Phase 1

Conditions: KRAS Gene Mutation; CRC; Solid Tumors; NSCLC

Treatments: Drug: Telaglenestat (CB-839); Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Study type: Interventional

Funder types: Industry

Identifiers

NCT03965845

CX-839-012

Details and patient eligibility

About

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.

Enrollment: 53 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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:

  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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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53 participants in 5 patient groups

Cohort 1: Telaglenastat 600 mg and Palbociclib 75 mg

Experimental group

Treatment:

Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Drug: Telaglenestat (CB-839)

Cohort 2: Telaglenastat 800 mg and Palbociclib 75 mg

Experimental group

Treatment:

Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Drug: Telaglenestat (CB-839)

Cohort 3: Telaglenastat 800 mg and Palbociclib 100 mg

Experimental group

Treatment:

Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Drug: Telaglenestat (CB-839)

Cohort 3: Telaglenastat 800 mg and Palbociclib 125 mg

Experimental group

Treatment:

Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Drug: Telaglenestat (CB-839)

Part 2: Expansion

Experimental group

Description:

The recommended phase 2 dose (RP2D) determined from Part 1 will be the treatment for all cohorts in expansion Part 2.

Treatment:

Drug: Palbociclib Oral Capsule or Tablet [Ibrance]

Drug: Telaglenestat (CB-839)