A Study of D3S 001 Monotherapy or Combination Therapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation

A Phase 1/2, Open Label, Dose-escalation, and Dose-expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of D3S 001 Monotherapy or Combination Therapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation

This is a first-in-human (FIH), multicenter, open-label, dose-escalation, and dose-expansion Phase 1/2 clinical trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of D3S-001 or combination therapy in subjects with advanced KRAS p.G12C mutant solid tumors. D3S-001 will be taken daily by oral administration in 21-day treatment cycles.

Study Overview

• Status: Recruiting
• Conditions: KRAS P.G12C
• Intervention / Treatment: Drug: Carboplatin; Drug: Cisplatin; Drug: Pembrolizumab; Drug: Cetuximab; Drug: D3S-001; Drug: Pemetrexed

• Study Type: Interventional
• Enrollment (Estimated): 352
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Director; Phone Number: +86 21 61635900; Email: D3bio_CT@d3bio.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2109
      • Recruiting
      • D3 Bio Investigative Site
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • Recruiting
      • D3 Bio Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • D3 Bio Investigative Site
• China
  • Beijing
    • Beijing, Beijing, China, 100036
      • Recruiting
      • D3 Bio Investigative Site
  • Hangzhou
    • Hangzhou, Hangzhou, China, 310022
      • Recruiting
      • D3 Bio Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Recruiting
      • D3 Bio Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 43000
      • Recruiting
      • D3 Bio Investigative Site
    • Wuhan, Hubei, China, 430079
      • Recruiting
      • D3 Bio Investigative Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330008
      • Recruiting
      • D3 Bio Investigative Site
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Recruiting
      • D3 Bio Investigative Site
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • D3 Bio Investigative Site
    • Shanghai, Shanghai, China, 201801
      • Recruiting
      • D3 Bio Investigative Site
• Hong Kong
  • Sha Tin, Hong Kong, 999077
    • Recruiting
    • D3 Bio Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • D3 Bio Investigative Site
  • Seoul, Korea, Republic of, 120-752
    • Recruiting
    • D3 Bio Investigative Site
  • Seoul, Korea, Republic of, 138-736
    • Recruiting
    • D3 Bio Investigative Site
  • North Chungcheong
    • Cheongju-si, North Chungcheong, Korea, Republic of, 28644
      • Recruiting
      • D3 Bio Investigative Site
• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • D3 Bio Investigative Site
  • Michigan
    • Detroit, Michigan, United States, 48202-2608
      • Recruiting
      • D3 Bio Investigative Site
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • D3 Bio Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion:

• Subject must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor which is progressing.
• Subject must have documented KRAS p.G12C mutation identified within the last 5 years by a local test on tumor tissue or blood.
• Subject must have measurable disease per RECIST v1.1.
• Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subject must have adequate organ and marrow function within the screening period.

Exclusion:

• Subject has any prior treatment with other treatments without adequate washout periods as defined in the protocol.
• Subject has uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the subject to give written informed consent.
• Subject has unresolved treatment-related toxicities from previous anticancer therapy of NCI CTCAE Grade ≥2 (with exception of vitiligo or alopecia).
• Subject has active gastrointestinal disease or other that could interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy.
• Concurrent participation in any clinical research study involving treatment with any investigational drug, radiotherapy, or surgery, except for the nontreatment phases of these studies (e.g., follow-up phase).

Other protocol inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D3S-001 monotherapy; Part 1: Dose Escalation, D3S-001 administered orally. Part 2 and Part 3a Arm C: Dose Expansion, D3S-001 administered orally in selected cancer type patients.	Drug: D3S-001; Oral
Experimental: D3S-001 and pembrolizumab; Part 3a Arm A: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Pembrolizumab administered intravenously.	Drug: Pembrolizumab; Intravenous; Drug: D3S-001; Oral
Experimental: D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + permetrexed); Part 3a Arm B: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cisplatin + pemetrexed administered intravenously or Carboplatin + permetrexed administered intravenously	Drug: Carboplatin; Intravenous; Drug: Cisplatin; Intravenous; Drug: D3S-001; Oral; Drug: Pemetrexed; Intravenous
Experimental: D3S-001 and Cetuximab; Part 3b: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cetuximab administered intravenously.	Drug: Cetuximab; Intravenous; Drug: D3S-001; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events (AEs)	From first dose until 30 days after the last dose (or specified in the protocol).
Number of Participants With Dose-Limiting Toxicities (DLTs)	From Cycle 1 Day 1 through Day 21. Each cycle is 21 days.

Secondary Outcome Measures

Outcome Measure	Time Frame
D3S-001 maximum observed plasma concentration (Cmax)	Up to 24 months.
D3S-001 time to maximum plasma concentration (tmax)	Up to 24 months.
D3S-001 half-life (t1/2)	Up to 24 months.
D3S-001 area under the concentration-time curve (AUC)	Up to 24 months.
Objective response rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)	Up to 24 months.
Duration of Response (DOR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)	Up to 24 months.
Progression-free survival (PFS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)	Up to 24 months.
Disease Control Rate (DCR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)	Up to 24 months.

Collaborators and Investigators

• Sponsor: D3 Bio (Wuxi) Co., Ltd
• Investigators: Study Director: Cheng Chen, MD, D3 Bio (Wuxi) Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 8, 2022

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 31, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: advanced solid tumors; Mutation; KRAS p.G12C
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Pembrolizumab; Pemetrexed; Cetuximab
• Other Study ID Numbers: D3S-001-100; 2023-508517-16 (EudraCT Number)

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