Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
Conditions
Interventions
Experimental: Part 1a: Dose Escalation monotherapy
Experimental: Part 1b: Dose Expansion monotherapy
Experimental: Part 1c: Pharmacodynamic cohort
Experimental: Part 2a: Dose Escalation combination
Ex
Sponsors
Ono Shintaro
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. >=18 years old 2. Locally-advanced or metastatic solid tumor with KRAS G12D mutation 3. For Part 1 and Part 2 Combination Groups 1 and 2: Disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, or no available standard treatment to improve the disease outcome 4. For Part 2 Combination Groups 3 and 4: No more than 1 prior standard treatment 5. Cohort specific requirements as follows: 5.1. Part 1A and 1D: Histologically or cytologically confirmed malignant solid tumor of any tissue origin 5.2. Part 1B 5.2.1. Disease group 1: diagnosis of PDAC and <= 2 prior standard systemic regimens for pancreatic cancer 5.2.2. Disease group 2: diagnosis of CRC 5.2.3. Disease group 3: diagnosis of NSCLC 5.2.4. Disease group 4: diagnosis of other advanced solid tumor and not part of Disease groups 1, 2 or 3 5.3. Part 1c: Confirmed diagnosis of PDAC, CRC, or NSCLC 5.4. Parts 2A and 2B 5.4.1. Combination 1: Diagnosis of PDAC or Diagnosis of CRC and 5.4.1.1. Prior treatment in the advanced setting with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan and 5.4.1.2. In Part 2a: <=3 prior standard regimens 5.4.1.3. In Part 2b: <=2 prior standard regimens 5.4.2. Combination 2: Diagnoses of PDAC, CRC or NSCLC 5.4.3. Combination Group 3 (INCB161734 in combination with GEMNabP) and Combination Group 4 (INCB161734 in combination with mFOLFIRINOX): 5.4.3.1. Diagnosis of PDAC 5.4.3.2. <= 1 prior standard systemic regimen for pancreatic cancer 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
Exclusion criteria: 1. Prior treatment with any KRAS G12D inhibitor 2. Known additional invasive malignancy within 1 year of the first dose of study drug 3. History of organ transplant, including allogeneic stem cell transplantation 4. Significant, uncontrolled medical condition 5. History or presence of an ECG abnormality 6. Inadequate organ function Other protocol-defined Inclusion/Exclusion Criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Number of participants with Dose Limiting Toxicities (DLTs) [Time Frame: Up to 28 days] 2. Number of participants with Treatment-emergent Adverse Events (TEAEs) [Time Frame: Up to 2 years and 90 days] 3. Number of participants with TEAEs leading to dose modification or discontinuation [Time Frame: Up to 2 years and 90 days] | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. INCB161734 pharmacokinetic (PK) in Plasma [Time Frame: Up to approximately 90 days] 2. Objective Response Rate (ORR) [Time Frame: Up to 2 years] 3. Disease Control Response (DCR) [Time Frame: Up to 2 years] 4. Duration of Response (DOR) [Time Frame: Up to 2 years] | — |
Countries
Australia, Belgium, Canada, France, Italy, Japan, Spain, United States
Contacts
Public ContactMedical Information Center
Incyte Biosciences Japan G.K.
Outcome results
None listed