D3S-001 for KRAS Mutation-related Cancer

Recruiting in Palo Alto (17 mi)

+33 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: D3 Bio (Wuxi) Co., Ltd

Disqualifiers: Cardiovascular disease, Gastrointestinal conditions, others

No Placebo Group

Breakthrough Therapy

Approved in 8 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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.

What makes the drug D3S-001 unique for treating KRAS mutation-related cancer?

D3S-001 is unique because it targets KRAS mutations, which are common in certain cancers like colorectal and non-small cell lung cancer, and are known to be resistant to many existing treatments. This drug may offer a new approach for patients with these mutations, who typically have limited options and poorer outcomes with standard therapies. ^{1 2 3 4 5}

Research Team

Cheng Chen, MD

Principal Investigator

D3 Bio (Wuxi) Co., Ltd

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• D3S-001 (Small Molecule)

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.

Participant Groups

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.

Group II: D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + permetrexed) 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 + permetrexed 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 China for the following indications:

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+

Findings from Research

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]

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]

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]

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]

References

1. India 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. [2022]

2. Singapore pubmed.ncbi.nlm.nih.gov

Untangling the KRAS mutated lung cancer subsets and its therapeutic implications. [2022]

3. United States 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. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

KRAS mutations in non-small cell lung cancer. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Significance of K-ras detection in colorectal cancer]. [2010]