What side effects are associated with this type of intervention?

Common side effects of treatments targeting the KRAS p.G12C mutation, such as sotorasib and adagrasib, include gastrointestinal issues (nausea, diarrhea), fatigue, liver enzyme elevations, and musculoskeletal pain. These side effects are generally manageable but can vary in severity. The D3S-001 trial, which is evaluating a similar targeted therapy, will likely observe comparable adverse effects, focusing on safety and tolerability in its early phases.

What prior FDA approvals exist?

The FDA has approved several drugs targeting KRAS mutations, particularly the KRAS p.G12C mutation. Sotorasib (Lumakras) was the first FDA-approved drug specifically targeting KRAS p.G12C mutation in non-small cell lung cancer (NSCLC). Another drug, adagrasib, is also being developed for similar indications. These drugs work by inhibiting the KRAS G12C protein, thereby blocking the signaling pathways that promote cancer cell growth. These treatments are similar to the investigational drug D3S-001, which is being studied for its efficacy in advanced solid tumors with the KRAS p.G12C mutation.

What other types of research exist?

Promising alternatives to D3S-001 for KRAS mutation patients include investigational agents targeting the KRAS pathway, such as adagrasib (MRTX849) and sotorasib (AMG 510). Both have shown efficacy in clinical trials for KRAS p.G12C mutant cancers. Additionally, combination therapies involving MEK inhibitors or other targeted agents may offer potential benefits.

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Small Molecule

D3S-001 for KRAS Mutation-related Cancer

Phase 1 & 2

Recruiting

Research Sponsored by D3 Bio (Wuxi) Co., Ltd

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Subject must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor which is progressing

Must not have

Subject has any prior treatment with other treatments without adequate washout periods as defined in the protocol

Subject has uncontrolled intercurrent illness, including 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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, D3S-001, taken daily for a few weeks, in patients with certain advanced cancers. The drug aims to block a faulty part of the cancer cells to stop or slow their growth.

Who is the study for?

This trial is for adults with advanced solid tumors that have a specific genetic change called KRAS p.G12C mutation. They must show measurable disease progression, be relatively fit (ECOG status of 0 or 1), and have good organ and marrow function. People can't join if they're still experiencing significant side effects from previous cancer treatments, are in other treatment studies, haven't waited long enough after past treatments, or have illnesses that could affect the study drug's action or their participation.

What is being tested?

The trial is testing D3S-001 as a solo treatment to see how safe it is and how well people tolerate it. It will also look at how the body processes the drug and its effect on tumors in patients with advanced solid tumors carrying the KRAS p.G12C mutation. The goal is to find out the best dose for Phase 2 trials.

What are the potential side effects?

Since this is a first-in-human study for D3S-001, potential side effects aren't fully known yet but may include typical reactions seen with cancer drugs such as nausea, fatigue, blood count changes, liver enzyme elevations, and possibly others based on how it affects tumor cells.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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My cancer is spreading and has been confirmed by a lab test.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not had recent treatments without following the required break period.

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I do not have any serious illnesses or conditions that would stop me from following the study rules.

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I don't have serious side effects from cancer treatment, except for hair loss or skin color changes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: D3S-001 monotherapyExperimental Treatment1 Intervention

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.

Group II: D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + permetrexed)Experimental Treatment4 Interventions

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

Group III: D3S-001 and pembrolizumabExperimental Treatment2 Interventions

Part 3a Arm A: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Pembrolizumab administered intravenously.

Group IV: D3S-001 and CetuximabExperimental Treatment2 Interventions

Part 3b: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cetuximab administered intravenously.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

Cisplatin

2013

Completed Phase 3

~3120

Carboplatin

2014

Completed Phase 3

~6120

Cetuximab

2011

Completed Phase 3

~2480

Pemetrexed

2014

Completed Phase 3

~5550

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

KRAS p.G12C mutations are targeted by specific inhibitors that covalently bind to the mutant cysteine residue in the KRAS protein, locking it in an inactive GDP-bound state. This prevents the activation of downstream signaling pathways that promote tumor growth and survival. Treatments like sotorasib and adagrasib are examples of such inhibitors. These therapies are significant for KRAS p.G12C mutation patients because they offer a targeted approach to disrupt the oncogenic signaling driven by the mutant KRAS, potentially leading to better clinical outcomes compared to traditional chemotherapy.