Advanced Solid Tumors, Cancer, CRC (Colorectal Cancer), NSCLC (Non-small Cell Lung Cancer), PDAC - Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
KRAS mutation, NSCLC, Non-small cell lung cancer, Colorectal cancer, Pancreatic ductal adenocarcinoma, Colorectal carcinoma, Pancreatic cancer, Pancreatic carcinoma, Solid tumors, KRAS, Mutation, Metastatic, Advanced unresectable, Neoplasms, Neoplasms by Site, Carcinoma, Non-small cell lung carcinoma, Non-small cell lung neoplasm, Pancreatic neoplasm, Lung neoplasm, Colorectal neoplasm, Colon neoplasm, Mutant KRAS, KRAS amplification
Brief summary
The purpose of this study is to characterize the safety and tolerability of ALTA3263 in adults with advanced solid tumors with KRAS mutations.
Detailed description
This is an open-label, multicenter, Phase 1/1b study of ALTA3263, an orally bioavailable KRAS isoform-selective inhibitor that inhibits multiple mutant forms of KRAS, in adults with advanced solid tumor malignancies with KRAS mutations. This study will evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity of ALTA3263 as a monotherapy and as a combination regimen. The study consists of two parts: Part 1 - Dose Escalation and Part 1b - Dose Expansion.
Interventions
DRUGALTA3263
Oral ALTA3263 tablets will be administered at a protocol-defined dose
DRUGcetuximab
Cetuximab injection for IV use will be administered at a protocol-defined dose
DRUGmFOLFOX6
modified folinic acid (leucovorin), fluorouracil, and oxaliplatin will be administered at a protocol-defined dose
DRUGPembrolizumab
Pembrolizumab injection for IV use will be administered at a protocol-defined dose
Pemetrexed and carboplatin/cisplatin injection for IV use will be administered at a protocol-defined dose
DRUGmFOLFIRINOX
modified folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin will be administered at a protocol-defined dose
DRUGGnP
gemcitabine and albumin-bound paclitaxel will be administered at a protocol-defined dose
DRUGMidazolam
Oral midazolam will be administered at a protocol-defined dose
Sponsors
Alterome Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of a solid tumor malignancy harboring a KRAS mutation identified through molecular testing (NGS- or PCR-based) with a Clinical Laboratory Improvement Amendments-certified (or equivalent) diagnostic test. * Unresectable or metastatic disease. * Progressed on, intolerant to, or declined prior standard-of-care therapy (including targeted therapy, if applicable) appropriate to tumor type and stage * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate organ function
Exclusion criteria
* Prior treatment with a KRAS inhibitor, certain exceptions are described in the full study protocol * Known condition that prohibits the ability to swallow or absorb an oral medication. Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Up to 39 months | Number of participants that experience treatment-emergent adverse events (TEAEs). |
| Dose Limiting Toxicities | 21 days | Number of participants with Dose Limiting Toxicities (DLTs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (each cycle is 21 days) Day 1 (or Lead-in) and Day 15: Predose and up to 24 hours postdose | Cmax |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Cycle 1 (each cycle is 21 days) Day 1 (or Lead-in) and Day 15: Predose and up to 24 hours postdose | Tmax |
| Area Under Plasma Concentration Time Curve During the Dosing Interval (AUCt) | Cycle 1 (each cycle is 21 days) Day 1 (or Lead-in) and Day 15: Predose and up to 24 hours postdose | AUCt |
| Terminal Half-Life (t1/2) | Cycle 1 (each cycle is 21 days) Lead-in phase: Predose and up to 48 hours postdose | t1/2 |
| Objective Response Rate (ORR) | Up to 39 months | Assess per RECIST 1.1 |
| Duration of Response (DOR) | Up to 39 months | Assess per RECIST 1.1 |
| Progression-Free Survival (PFS) | Up to 39 months | Assess per RECIST 1.1 |
| Overall Survival (OS) | Up to 39 months | Assess per RECIST 1.1 |
Countries
United States
Contacts
CONTACTAlterome Clinical Trial Contact Center
STUDY_DIRECTORStudy Medical Director
Alterome Therapeutics
Outcome results
None listed