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.12345
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.
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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.
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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 OverviewThe 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
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.
D3S-001 is already approved in United States, China, Australia 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
🇦🇺 Approved in Australia as D3S-001 for:
- Advanced solid tumors with KRAS G12C mutation
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
D3 Bio Investigative SiteHouston, TX
D3 Bio Investigative SiteDenver, CO
D3 Bio Investigative SiteSarasota, FL
D3 Bio Investigative SiteNashville, TN
More Trial Locations
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Who Is Running the Clinical Trial?
D3 Bio (Wuxi) Co., LtdLead Sponsor
References
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]The requirement for the mutation analysis for Kirsten rat sarcoma viral oncogene (KRAS) in colorectal cancer (CRC) is rapidly increasing as it is a predictive biomarker and also, its absence signifies response to anti-epidermal growth factor receptor (anti-EGFR) antibody treatment. The aim of our study was to investigate the pathological diagnosis and distribution of KRAS mutations in colorectal cancer with the use of next generation sequencing platform (Ion Torrent).
Untangling the KRAS mutated lung cancer subsets and its therapeutic implications. [2022]The Kirsten rat sarcoma virus transforming protein (KRAS) mutations (predominate in codons 12, 13, and 61) and genomically drive nearly one-third of lung carcinomas. These mutations have complex functions in tumorigenesis, and influence the tumor response to chemotherapy and tyrosine kinase inhibitors resulting in a poorer patient prognosis. Recent attempts using targeted therapies against KRAS alone have met with little success. The existence of specific subsets of lung cancer based on KRAS mutations and coexisting mutations are suggested. Their interactions need further elaboration before newer promising targeted therapies for KRAS mutant lung cancers can be used as earlier lines of therapy. We summarize the existing knowledge of KRAS mutations and their coexisting mutations that is relevant to lung cancer treatment, in this review. We elaborate on the prognostic impact of clinical and pathologic characteristics of lung cancer patients associated with KRAS mutations. We briefly review the currently available techniques for KRAS mutation detection on biopsy and cytology samples. Finally, we discuss the new therapeutic strategies for targeting KRAS-mutant non-small cell lung cancer (NSCLC). These may herald a new era in the treatment of KRASG12Cmutated NSCLC as well as be helpful to develop demographic subsets to predict targeted therapies and prognosis of lung cancer patients.
A commercial real-time PCR kit provides greater sensitivity than direct sequencing to detect KRAS mutations: a morphology-based approach in colorectal carcinoma. [2018]KRAS mutation testing has become a standard procedure in the management of patients with carcinomas. The most frequently used method for KRAS testing is direct sequencing of PCR products. The development of commercial real-time quantitative PCR kits offers a useful alternative since they are in theory much more sensitive than direct sequencing and they avoid post- PCR handling. We present our experience as a reference center for the study of KRAS mutations, comparing direct sequencing and the use of a commercial real-time quantitative PCR kit, as well as determining the sensitivity of both procedures in clinical practice. The TheraScreen K-RAS Mutation Kit identified mutations in 75 (44%) of the 170 tumors. Three cases were tested positive using TheraScreen K-RAS Mutation Kit and negative by direct sequencing. We then compared the sensitivity of the kit and that of direct sequencing using 74 mutant tumors. The kit was able to detect the presence of a mutation in a 1% dilution of the total DNA in 13.5% of the tumors and, in 84%, KRAS mutation was identified at a dilution of 5%. Sequencing was able to detect KRAS mutations when the mutant DNA represented 10% of the total DNA in 20/74 (27%) of the tumors. When the mutant DNA represented 30% of the total DNA, sequencing could detect mutations in 56/74 (76%).
KRAS mutations in non-small cell lung cancer. [2022]Some non-small cell lung cancers (NSCLCs) harbor a single specific mutated oncogene that is thought to be the primary genetic "driver" leading to cancer. The two most commonly mutated oncogenes in lung cancer encode for the epidermal growth factor receptor (EGFR) and KRAS. EGFR kinase domain mutations were only recently identified, but they have already been established in the clinic as valid predictors of increased sensitivity to EGFR kinase inhibitors (gefitinib and erlotinib). By contrast, even though KRAS mutations were identified in NSCLC tumors more than 20 years ago, we have only just begun to appreciate the clinical value of KRAS tumor status. Recent studies indicate that patients with mutant KRAS tumors fail to benefit from adjuvant chemotherapy, and their disease does not respond to EGFR inhibitors. There is a dire need for therapies specifically for patients with KRAS mutant NSCLC. In this review, we summarize the initial discovery of RAS mutations in NSCLC, describe work exploring associations with clinical factors and outcomes, and provide an overview of current approaches to targeting KRAS mutant NSCLC.
[Significance of K-ras detection in colorectal cancer]. [2010]To determine the mutation status of K-ras gene in colorectal cancer and analyze the associations between its mutation status and clinicopathological characteristics in colorectal cancer so as to select the patients likely to benefit from a targeted therapy.