A Phase II Study of GFH375 Combined With GFS202A or GFH276 Versus GFH375 Monotherapy in Patients With Previously Treated Locally Advanced Unresectable or Metastatic Pancreatic Cancer Harboring KRAS G12D Mutation

Phase 2Not Yet RecruitingNCT07784374

Genfleet Therapeutics (Shanghai) Inc.120 enrolled

Overview

This is a phase 2 study. All subjects are patients with locally advanced unresectable or metastatic pancreatic cancer harboring KRAS G12D mutation who have received at least one prior line of systemic therapy. The purpose of this study is to evaluate the anti-tumor efficacy of GFH375 plus GFH276 versus GFH375 monotherapy, and to assess the impact of GFH375 plus GFS202A versus GFH375 monotherapy on patient body weight.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

120

Conditions

Pancreatic Cancer

Interventions

GFH375DRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Able to provide written informed consent prior to any study-related procedures. * Male or female subjects aged between 18 and 80 years (inclusive) at the time of informed consent. * Histologically or cytologically confirmed pancreatic adenocarcinoma. * Estimated life expectancy ≥ 3 months as judged by the investigator. * Has received at least 1 prior line of systemic anti-tumor therapy. * Has at least one measurable lesion per RECIST version 1.1. * Adequate organ function. Exclusion Criteria: * Other malignancy that has progressed or required treatment within 3 years prior to study entry. * Active central nervous system (CNS) metastases. * Prior treatment with KRAS G12D-specific or pan-RAS/KRAS targeted agents. * Clinically significant severe cardiovascular disease. * Stroke or other severe cerebrovascular events within 6 months prior to randomization. * Significant acute or chronic infectious disease. * Severe psychiatric disorder, history of drug abuse, or significant alcohol abuse. * Pregnant or lactating female subjects. * Other conditions that, in the investigator's opinion, make the subject unsuitable for study participation.

Outcomes

Primary Outcomes

PFS

Progression-Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) according to RECIST v1.1

Time frame: Up to approximately 2 years

Weight

Percentage Change in Body Weight From Baseline at Week 12

Time frame: Baseline, From first study treatment to Week 12

Secondary Outcomes

Overall Survival (OS)

Time frame: Up to approximately 3 years

PFS

Progression-Free Survival (PFS) Assessed by Investigator per RECIST Version 1.1

Time frame: Up to approximately 2 years

ORR

Objective Response Rate (ORR), Assessed by Blinded Independent Central Review (BICR) and Investigator per RECIST Version 1.1

Time frame: Up to approximately 2 years

DCR

Disease Control Rate (DCR)Assessed by Blinded Independent Central Review (BICR) and Investigator per RECIST Version 1.1

Time frame: Up to approximately 2 years

DoR

Duration of Response (DoR)Assessed by Blinded Independent Central Review (BICR) and Investigator per RECIST Version 1.1

Time frame: Up to approximately 2 years

TTR

Time-to-Response (TTR) Assessed by Blinded Independent Central Review (BICR) and Investigator per RECIST Version 1.1

Time frame: Up to approximately 2 years

FAACT Scores

Change from Baseline in FAACT-A/CS and FAACT-A/CS-5-Item Anorexia Symptom Scale (5IASS) Scores

Time frame: Up to approximately 2 years

L3SMI

Change from Baseline in Third-Lumbar-Level Skeletal Muscle Index (L3SMI)

Time frame: Up to approximately 2 years

Change in third-lumbar-level fat area

Change in Third-Lumbar-Level Intermuscular Fat Area, Subcutaneous Fat Area and Visceral Fat Area

Time frame: Up to approximately 2 years

The incidence and severity of AEs and SAEs

Time frame: Up to approximately 2 years

Plasma concentration of GFH375

Trough concentration of GFH375

Time frame: Up to approximately 2 years

Plasma concentration of GFH276

Trough concentration of GFH276

Time frame: Up to approximately 2 years

Plasma concentration of GFS202A

Trough concentration of GFS202A

Time frame: Up to approximately 2 years

A Phase II Study of GFH375 Combined With GFS202A or GFH276 Versus GFH375 Monotherapy in Patients With Previously Treated Locally Advanced Unresectable or Metastatic Pancreatic Cancer Harboring KRAS G12D Mutation

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts