Testing D3S-003 alone in people with advanced solid tumors that have a KRAS p.G12D mutation

A Phase 1, Open-label, Dose-Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of D3S-003 Monotherapy in Participants With Advanced Solid Tumors With a KRAS p.G12D Mutation

This trial will test whether D3S-003 given by itself is safe and shows signs of benefit for people with advanced solid tumors that carry a KRAS p.G12D mutation who have already tried at least one standard therapy.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: D3 Bio (Wuxi) Co., Ltd (industry)
• Locations: 1 site (San Antonio, Texas)
• Trial ID: NCT07456046 on ClinicalTrials.gov

What this trial studies

This first-in-human, open-label, dose-escalation Phase 1 trial gives D3S-003 as a single agent to adults with advanced solid tumors that harbor a KRAS p.G12D mutation. The study will escalate doses to define safety, tolerability, and the recommended dose while collecting pharmacokinetic and pharmacodynamic data. Eligible participants must have measurable disease, ECOG performance status 0–1, adequate organ function, and have progressed after prior standard therapy. Preliminary anti-tumor activity will be monitored using RECIST v1.1 alongside safety assessments.

Who should consider this trial

Good fit: Adults with locally advanced, recurrent, or metastatic solid tumors confirmed to have a KRAS p.G12D mutation, measurable disease, ECOG 0–1, adequate organ and marrow function, and prior progression after at least one standard therapy are the best fit for this trial.

Not a fit: Patients who previously received a KRAS G12D or pan-RAS inhibitor/degrader, those with poor performance status (ECOG ≥2), uncontrolled serious illnesses, or without the KRAS p.G12D mutation are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, D3S-003 could become a targeted treatment option that specifically attacks tumors with the KRAS p.G12D mutation and may shrink tumors or slow disease progression for patients with few options.

How similar studies have performed: Direct KRAS G12D-targeted therapies are a novel approach with limited human data, although KRAS G12C inhibitors have demonstrated clinical activity and support the general strategy of mutation-specific KRAS targeting.

Eligibility criteria

Inclusion Criteria:

* Subjects must have histologically confirmed locally advanced, recurrent, or metastatic malignancy that has progressed following at least one line of standard therapy or where standard therapy has proven to be ineffective or intolerable or is considered inappropriate or when participation in a clinical trial of an investigational agent is considered a standard therapeutic option.
* Subjects must have documented presence of KRAS p.G12D mutation by a local test identified through tumor tissue or blood collected within the last 5 years.
* Subjects 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 Criteria:

* Participant has any prior treatment with a specific KRAS G12D inhibitor/degrader or pan RAS inhibitor/degrader.
* Subject has uncontrolled intercurrent illness, including but not limited to serious chronic gastrointestinal conditions associated with diarrhea, ongoing or active infections, uncontrolled or significant cardiovascular disease, autoimmune or inflammatory disorders or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events (AEs), or compromise the ability of the subject to give written consent.
* Uncontrolled or untreated brain metastases
* Subject has active gastrointestinal disease or other that could interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy

NOTE: Other protocol inclusion/exclusion criteria may apply.

Where this trial is running

San Antonio, Texas

• D3 Bio Investigative Site 1402 — San Antonio, Texas, United States (RECRUITING)

Study contacts

• Study coordinator: Medical Director

Conditions: KRAS P.G12D, KRAS P.G12D Mutation, Advanced solid tumors