Study of LT-010391 in Participants With KRAS G12D-Mutant Solid Tumors

A Phase I, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of LT-010391 Tablets in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation

This study is to evaluate the safety and tolerability of of LT-010391 as monotherapy in participants with KRAS G12D mutant advanced solid tumors

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumors; Non-small Cell Lung Cancer (NSCLC); Pancreatic Ductal Adenocarcinoma (PDAC); Colorectal Cancer (CRC)
• Intervention / Treatment: Drug: LT-010391

Detailed Description

This is an open-label, multicenter, Phase 1 study of LT-010391, a selective and orally bioavailable KRAS G12D degrader in participants with KRAS G12D mutant advanced solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two parts: Part A- dose escalation and Part B- dose expansion.

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Leadingtac Pharmaceutical (Shaoxing) Co., Ltd.; Phone Number: +86-21-50561622; Email: jxu@leadingtac.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
      • Contact: Zhengbo Song, MD; Phone Number: 86571-88122146; Email: irb@zjcc.org.cn
      • Principal Investigator: Zhengbo Song, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants with histologically or cytologically confirmed advanced solid tumors harboring a KRAS G12D mutation;
• Failed standard therapy, intolerant to standard therapy, or no standard therapy is available;
• ECOG Performance Status of 0 or 1;
• Adequate organ function

Exclusion Criteria:

• History of ≥2 primary malignancies within 5 years prior to signing informed consent, except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or other malignancies considered cured;
• Primary central nervous system (CNS) tumors
• leptomeningeal metastases, brainstem metastases, or spinal cord compression confirmed by imaging (regardless of symptoms) Other inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: A single arm study of LT-010391 including dose-escalation and dose-expansion cohorts; Part A: Dose Escalation Participants will receive the designated dose. Enrollment into dose escalation may be from any advanced solid tumors with KRAS G12D mutation. Part B: Dose Expansion: Upon completing DLT observation for a dose level, investigators and sponsor may discuss selecting a specific cancer type for expansion at prior dose.

Drug: LT-010391; LT-010391 tablets, oral, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities	Number of participants with Dose Limiting Toxicities (DLTs)	21 days
Adverse events	Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs, and vital signs	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters	Cmax will be recorded from the PK plasma samples collected.	up to 15 weeks
Overall Response Rate (ORR)	Assess per RECIST v1.1	up to 2 years
Duration of Response (DOR)	Assess per RECIST v1.1	up to 2 years
Disease Control Rate（DCR）	Assess per RECIST v1.1	up to 2 years
Progression-Free Survival (PFS)	Assess per RECIST v1.1	up to 2 years

Collaborators and Investigators

• Sponsor: Leadingtac Pharmaceutical (Shaoxing) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: May 24, 2026
• First Submitted That Met QC Criteria: May 31, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 31, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: LT010391US001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No