Phase 1, First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of KO-2806 When Administered as Monotherapy and in Combination Therapy in Adult Patients with Advanced Solid Tumors
Primary - Safety:
To evaluate the safety and tolerability of KO-2806 when administered as monotherapy and in combination therapy in patients with advanced solid tumors (escalation phases)
To determine the maximum tolerated dose (MTD)and/or the optimal biologically active dose (OBAD) of KO-2806 when administered as monotherapy and in combination therapy in patients with advanced solid tumors (escalation phases)
To define the recommended Phase 2 dose (RP2D) of KO-2806 in combination therapy in patients with advanced solid tumors (expansion phase)
Primary - efficacy:
To evaluate the antitumor activity of KO-2806 when administered in combination therapy in patients with advanced solid tumors (expansion phase)
Secondary - safety:
To further evaluate the safety and tolerability of KO-2806 when administered in combination therapy in patients with advanced solid tumors (expansion phase)
Secondary - Efficacy
To evaluate the preliminary antitumor activity of KO-2806 when administered as monotherapy or in combination therapy in patients with advanced solid tumors (escalation phases
To further evaluate the antitumor activity of KO-2806 when administered in combination therapy in patients with advanced solid tumors (expansion phase)
Other Secondary:
To characterize the PK of KO-2806 when administered as monotherapy and the PK of KO-2806 and the combination agent when administered in combination therapy (escalation and expansion parts)
Cabozantinib (XL184)
KO-2806
- Rutgers University
Inclusion Criteria: - At least 18 years of age. - Histologically or cytologically confirmed advanced solid tumors - Arm #1 (Monotherapy): HRAS-mutant and/or amplified tumors (any solid tumor type); HRAS overexpression (only for HNSCC tumors); KRAS and/or NRAS, and/or HRAS-mutant and/or amplified NSCLC or CRC; KRAS-mutant and/or amplified PDAC - Arm #2 (Combination): Must have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC - Arm #3 (Combination): Must have KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC and have received at least 1 prior systemic therapy for advanced or metastatic disease - Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. - Karnofsky Performance Status of 70 or higher with no clinically significant deterioration over the previous 2 weeks. - Acceptable liver, renal, endocrine, and hematologic function. - Other protocol-defined inclusion criteria may apply. Exclusion Criteria: - Ongoing treatment with certain anticancer agents. - Prior treatment with an FTI or HRAS inhibitor. - Major surgery, other than local procedures, within 28 days prior to Cycle 1 Day 1, without complete recovery. - Spinal cord compression, leptomeningeal disease, or clinically active CNS metastases. - Toxicity (excluding alopecia) from prior therapy that has not been completely resolved to baseline at the time of consent. - Active or prior documented autoimmune or inflammatory disorders within the past 5 years prior to Cycle 1 Day 1 (with exceptions). - Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy. - Inability to swallow, impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs. - Inadequate cardiac and/or vascular function, including receipt of treatment for unstable angina, myocardial infarction, and/or cerebro-vascular attack within the prior 6 months, mean QTcF ≥470 ms, or Class II or greater congestive heart failure. - Other invasive malignancy within 2 years. - Other protocol-defined exclusion criteria may apply.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
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