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

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