D3S-001 for KRAS Mutation-related Cancer

Recruiting at 94 trial locations

Overseen By Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: D3 Bio (Wuxi) Co., Ltd

Disqualifiers: Cardiovascular disease, Gastrointestinal conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 8 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: 21 days per cycle

442 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, D3S-001 (an experimental treatment), for individuals with advanced cancers that have a specific genetic change called the KRAS p.G12C mutation. The goal is to determine if D3S-001 is safe and effective, both alone and in combination with other cancer treatments like pembrolizumab, chemotherapy, or cetuximab. Individuals diagnosed with a progressing solid tumor and the KRAS p.G12C mutation might be suitable for this trial. Participants will contribute to researchers' understanding of how D3S-001 functions and its potential as a treatment option for this type of cancer. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that prior treatments need adequate washout periods (time without taking certain medications). It's best to discuss your current medications with the trial team to understand any specific requirements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that D3S-001, a new treatment for cancers with the KRAS G12C mutation, was safe in earlier studies. Patients with certain cancers, such as non-small cell lung cancer and colorectal cancer, tolerated the treatment well in these studies. The FDA has also given the drug special recognition, often indicating promise in early safety and effectiveness.

For those considering joining a trial with D3S-001, either alone or with other drugs like pembrolizumab, platinum-based chemotherapy, or cetuximab, it's important to know that the current trial is in an early stage. This stage helps researchers understand the treatment's safety and how well people tolerate it. While early trials mainly focus on safety, the advancement of D3S-001 to this stage and its special FDA recognition are positive signs regarding its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for KRAS mutation-related cancers, which typically involve traditional chemotherapy and targeted therapies, D3S-001 introduces a novel approach by being an oral treatment that can be used alone or in combination with other drugs. One exciting feature is its potential to enhance the effectiveness of existing therapies like pembrolizumab, platinum doublet chemotherapy, and cetuximab, potentially leading to better outcomes. Researchers are particularly interested in D3S-001's ability to target specific cancer pathways, which may offer a more personalized treatment option and could lead to fewer side effects compared to conventional treatments.

What evidence suggests that this trial's treatments could be effective for KRAS mutation-related cancer?

Research has shown that D3S-001 could effectively treat cancers with KRAS G12C mutations. In previous studies, 60% of patients experienced tumor shrinkage, and 80% had their cancer growth slowed or stopped, indicating that the treatment controlled the disease in many patients. In this trial, participants may receive D3S-001 with pembrolizumab, which aims to enhance results by aiding the immune system in fighting cancer. Other participants will receive D3S-001 with either platinum doublet chemotherapy or cetuximab to evaluate if these combinations are more effective. While early results are promising, further research is needed to confirm these findings. ^{1 2 4 6 7}

Who Is on the Research Team?

Cheng Chen, MD

Principal Investigator

D3 Bio (Wuxi) Co., Ltd

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Subject must have measurable disease per RECIST v1.1

My cancer has a KRAS mutation identified in the last 5 years.

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

Exclusion Criteria

I am not currently in a study that involves new drug treatments, radiotherapy, or surgery.

I do not have stomach or bowel problems that could affect how medicine works in my body.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive D3S-001 monotherapy or combination therapy in 21-day treatment cycles

21 days per cycle

Visits every 21 days for treatment cycle

Dose Escalation

Dose escalation to determine the maximum tolerated dose of D3S-001

Varies

Dose Expansion

Dose expansion to further evaluate safety and efficacy at the determined dose

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• D3S-001

Trial Overview

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.

How Is the Trial Designed?

Group I: D3S-001 monotherapy Experimental Treatment 1 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. Part 4a: Dose Optimization, D3S-001 administered orally in selected cancer type patients.

Group II: D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + pemetrexed) Experimental Treatment 4 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 + pemetrexed administered intravenously

Group III: D3S-001 and pembrolizumab Experimental Treatment 2 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 Cetuximab Experimental Treatment 2 Interventions

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

D3S-001 is already approved in United States, China for the following indications:

Approved in United States as D3S-001 for:

• Advanced solid tumors with KRAS G12C mutation

Approved in China as D3S-001 for:

• Advanced solid tumors with KRAS G12C mutation

Who Is Running the Clinical Trial?

D3 Bio (Wuxi) Co., Ltd

Lead Sponsor

Trials

3

Recruited

560+

Published Research Related to This Trial

KRAS mutations, particularly in lung cancer, significantly affect tumor behavior and patient response to treatments, leading to poorer outcomes, and targeted therapies against KRAS have largely been unsuccessful so far.

Understanding the interactions between different KRAS mutations and coexisting mutations is crucial for developing effective targeted therapies, which may improve treatment options for patients with KRAS-mutant non-small cell lung cancer (NSCLC).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Untangling the KRAS mutated lung cancer subsets and its therapeutic implications. Ritu, K., Kumar, P., Singh, A., et al.[2022]

In a study of 208 colorectal cancer tissue samples, K-ras gene mutations were found in 91 cases, indicating a mutation rate of 43.8% at codons 12 or 13.

Identifying K-ras mutation status is crucial for selecting patients who may benefit from targeted therapies, such as monoclonal antibodies that target the epidermal growth factor receptor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Significance of K-ras detection in colorectal cancer]. Xu, XM., Zhang, GL., Li, MW., et al.[2010]

In a study of 56 colorectal cancer samples using next-generation sequencing, KRAS mutations were found in 44.6% of cases, indicating a high prevalence of this predictive biomarker for treatment response.

The most common KRAS mutations occurred in codon 12, particularly the p.Gly12Asp and p.Gly12Val substitutions, which are important for understanding the genetic landscape of colorectal cancer and guiding anti-EGFR therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The utility of the Ion Torrent PGM next generation sequencing for analysis of the most commonly mutated genes among patients with colorectal cancer in India. Mehra, S., Tiwari, AK., Mehta, SP., et al.[2022]

EGFR mutations in non-small cell lung cancer (NSCLC) are established as reliable indicators for sensitivity to EGFR inhibitors like gefitinib and erlotinib, highlighting their clinical importance.

In contrast, KRAS mutations, while known for over 20 years, have been shown to render patients unresponsive to both adjuvant chemotherapy and EGFR inhibitors, indicating a critical need for targeted therapies for KRAS mutant NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KRAS mutations in non-small cell lung cancer. Riely, GJ., Marks, J., Pao, W.[2022]

The TheraScreen K-RAS Mutation Kit identified KRAS mutations in 44% of the tumors tested, demonstrating its effectiveness as a sensitive method for detecting mutations compared to direct sequencing.

The kit was able to detect mutations at lower concentrations of mutant DNA (1% in 13.5% of cases and 5% in 84% of cases), while direct sequencing required at least 10% mutant DNA to identify mutations in only 27% of cases, highlighting the kit's superior sensitivity in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A commercial real-time PCR kit provides greater sensitivity than direct sequencing to detect KRAS mutations: a morphology-based approach in colorectal carcinoma. Angulo, B., García-García, E., Martínez, R., et al.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11372373/

D3S-001, a KRAS G12C Inhibitor with Rapid Target ...

However, the clinical outcomes of the first wave of KRAS G12C inhibitors seem to be suboptimal, with limited magnitude (ORR ranging from 30%–40% in NSCLC and 10 ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05410145

NCT05410145 | A Study of D3S-001 Monotherapy or ...

D3S-001 will be taken daily by oral administration in 21-day treatment cycles. Official Title. A Phase 1/2, Open Label, Dose-escalation, and Dose-expansion ...

3.

withpower.com

withpower.com/trial/phase-1-kras-pg12c-6-2022-fd3a1

D3S-001 for KRAS Mutation-related Cancer

KRAS mutations, particularly in lung cancer, significantly affect tumor behavior and patient response to treatments, leading to poorer outcomes, and targeted ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10970443/

Targeting KRAS G12C Mutation in Colorectal Cancer, A Review

All partial responses were accompanied by a reduction in circulating tumor DNA (ctDNA) KRAS G12C allele frequency to less than 1% after 2 cycles ...

5.

clinicaltrials.eu

clinicaltrials.eu/inn/d3s-001/

D3S-001 – Application in Therapy and Current Clinical ...

These combinations are being tested to see if they might be more effective than D3S-001 alone in treating advanced solid tumors with the KRAS G12C mutation.

6.

clinicaltrials.eu

clinicaltrials.eu/trial/study-on-the-safety-and-tolerability-of-d3s-001-alone-or-with-drug-combination-in-adults-with-advanced-solid-tumors-with-kras-p-g12c-mutation/

Study on the Safety and Tolerability of D3S-001 Alone or ...

The purpose of the study is to evaluate the safety and tolerability of D3S-001 in people with advanced solid tumors that have the KRAS p.G12C mutation.

7.

connect.careboxhealth.com

connect.careboxhealth.com/en-US/trial/listing/346663

A Study of D3S 001 Monotherapy or Combination Therapy in ...

Subject must have documented KRAS p.G12C mutation identified within the last 5 years by a local test on tumor tissue or blood.