A Study to Learn About Study Medicine ALTA3263 in Adults With Advanced Solid Tumors With KRAS Mutations

Alterome Therapeutics, Inc.

Status and phase: Enrolling; Phase 1

Conditions: PDAC - Pancreatic Ductal Adenocarcinoma; Advanced Solid Tumors; CRC (Colorectal Cancer); NSCLC (Non-small Cell Lung Cancer); Cancer

Treatments: Drug: Pembrolizumab; Drug: Pemetrexed + Cisplatin /Carboplatin; Drug: mFOLFIRINOX; Drug: GnP; Drug: mFOLFOX6; Drug: ALTA3263; Drug: Midazolam; Drug: cetuximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06835569

3263-001

Details and patient eligibility

About

The purpose of this study is to characterize the safety and tolerability of ALTA3263 in adults with advanced solid tumors with KRAS mutations.

Full 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.

Enrollment: 448 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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448 participants in 10 patient groups

ALTA3263 monotherapy

Experimental group

Description:

ALTA3263 will be administered continuously at a protocol-defined dose based on cohort assignment

Treatment:

Drug: ALTA3263

ALTA3263 in combination with cetuximab

Experimental group

Description:

ALTA3263 in combination with cetuximab will be administered continuously at a protocol-defined dose based on cohort assignment

Treatment:

Drug: cetuximab

Drug: ALTA3263

ALTA3263 in combination with mFOLFOX6 plus cetuximab

Experimental group

Description:

ALTA3263 in combination with modified folinic acid (leucovorin), fluorouracil, and oxaliplatin (mFOLFOX6) and cetuximab will be administered continuously at a protocol-defined dose based on cohort assignment

Treatment:

Drug: cetuximab

Drug: mFOLFOX6

Drug: ALTA3263

ALTA3263 in combination with pembrolizumab

Experimental group

Description:

ALTA3263 in combination with pembrolizumab will be administered continuously at a protocol-defined dose based on cohort assignment

Treatment:

Drug: ALTA3263

Drug: Pembrolizumab

ALTA3263 in combination with pembrolizumab plus chemotherapy

Experimental group

Description:

ALTA3263 in combination with pembrolizumab, pemetrexed, and carboplatin/cisplatin will be administered continuously at a protocol-defined dose based on cohort assignment

Treatment:

Drug: ALTA3263

Drug: Pemetrexed + Cisplatin /Carboplatin

Drug: Pembrolizumab

ALTA3263 in combination with mFOLFIRINOX

Experimental group

Description:

ALTA3263 in combination with modified folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) will be administered continuously at a protocol-defined dose based on cohort assignment

Treatment:

Drug: ALTA3263

Drug: mFOLFIRINOX

ALTA3263 in combination with mFOLFIRINOX plus cetuximab

Experimental group

Description:

ALTA3263 in combination with modified folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) plus cetuximab will be administered continuously at a protocol-defined dose based on cohort assignment

Treatment:

Drug: cetuximab

Drug: ALTA3263

Drug: mFOLFIRINOX

ALTA3263 in combination with GnP

Experimental group

Description:

ALTA3263 in combination with gemcitabine and albumin-bound paclitaxel will be administered continuously at a protocol-defined dose based on cohort assignment

Treatment:

Drug: ALTA3263

Drug: GnP

ALTA3263 in combination with GnP plus cetuximab

Experimental group

Description:

ALTA3263 in combination with gemcitabine, albumin-bound paclitaxel plus cetuximab will be administered continuously at a protocol-defined dose based on cohort assignment

Treatment:

Drug: cetuximab

Drug: ALTA3263

Drug: GnP

ALTA3263 Midazolam DDI Substudy

Experimental group

Description:

ALTA3263 and midazolam will be administered at a protocol defined schedule

Treatment:

Drug: Midazolam

Drug: ALTA3263