a study of telaglenastat (cb-839) in combination with palbociclib in patients with solid tumors

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

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

Keywords: tumor metabolism glutaminase inhibitor cb-839 palbociclib palbo telaglenestat cdk4/6 cdk4 cdk6