D3S-002 for Advanced Solid Tumors

Recruiting at 9 trial locations

Overseen By Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: D3 Bio (Wuxi) Co., Ltd

Must not be taking: Chemotherapy, Immunotherapy, Targeted therapy, others

Disqualifiers: Cardiovascular disease, Gastrointestinal conditions, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days per cycle

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any current cancer treatments, such as chemotherapy, immunotherapy, or targeted therapy, before participating. The protocol mentions a need for adequate washout periods (time without taking certain medications) from previous treatments, but it does not specify the exact duration.

What data supports the effectiveness of the drug D3S-002 for advanced solid tumors?

There is evidence that immune checkpoint inhibitors, a type of drug similar to D3S-002, are effective in treating advanced solid tumors, even in patients with poor health status, showing a disease control rate of 34.6% and good tolerance. ^{1 2 3 4 5}

What is the purpose of this trial?

This first-in-human (FIH) study aims to assess the safety, tolerability, pharmacokinetics, and recommended phase 2 dose (RP2D) of D3S-002 given orally daily for 21-day cycles in adult subjects with advanced solid tumors with mitogen-activated protein kinase (MAPK) pathway mutations.

Eligibility Criteria

Adults with advanced solid tumors showing MAPK pathway mutations, who have not responded to standard treatments or for whom no standard care exists. Participants must be in relatively good health (ECOG status 0-1) and have proper organ/marrow function. Those with ongoing serious illnesses, unresolved side effects from past cancer treatments, or conditions affecting drug absorption are excluded.

Inclusion Criteria

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

Standard treatments haven't worked for me or I can't tolerate them.

My cancer is advanced or has spread, and it's getting worse.

Exclusion Criteria

I do not have stomach or intestinal problems that could affect medication absorption.

I have not had recent treatments that conflict with the trial's requirements.

I do not have any serious illnesses that could interfere with the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive D3S-002 monotherapy orally daily for 21-day cycles

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• D3S-002

Trial Overview The trial is testing D3S-002, an oral medication taken daily over 21-day cycles. It's aimed at adults with specific genetic changes in their tumors that affect the MAPK pathway—a key signaling route that can lead to cancer growth when altered.

Participant Groups

Group I: D3S-002 Experimental Treatment 1 Intervention

Dose Escalation, D3S-002 administered orally.

D3S-002 is already approved in United States, China for the following indications:

Approved in United States as D3S-002 for:

• Advanced solid tumors with MAPK pathway mutations

Approved in China as D3S-002 for:

• Advanced solid tumors with MAPK pathway mutations

Who Is Running the Clinical Trial?

D3 Bio (Wuxi) Co., Ltd

Lead Sponsor

Trials

3

Recruited

560+

Findings from Research

Disease-free survival (DFS) is increasingly used as a key endpoint in clinical trials for cancer treatments, serving both as a surrogate and a primary endpoint, which influences regulatory decisions and clinical practices.

This commentary highlights the importance of understanding the history, assumptions, and limitations of DFS in evaluating recent drug approvals for anti-cancer agents in solid tumors, emphasizing its role in both adjuvant and curative treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease-free survival as an end-point in the treatment of solid tumours--perspectives from clinical trials and clinical practice. Robinson, AG., Booth, CM., Eisenhauer, EA.[2014]

A review of 76 phase III randomized controlled trials on advanced non-small cell lung cancer (NSCLC) from 2000 to 2012 showed a modest but continuous improvement in median overall survival, increasing by approximately 0.384 months per year, with a median overall survival of 9.90 months.

Despite the increase in patient sample sizes and the inclusion of molecular-targeted agents in trials, only 18.8% of the studies demonstrated a statistically significant improvement in overall survival, highlighting the need for careful evaluation of trial quality and outcomes before adopting new treatments in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in phase III randomized controlled clinical trials on the treatment of advanced non-small-cell lung cancer. Fernández-López, C., Expósito-Hernández, J., Arrebola-Moreno, JP., et al.[2021]

In a study of 97 women with high-risk breast cancer, there was no significant difference in overall survival (OS) or disease-free survival (DFS) between those receiving high-dose chemotherapy and those receiving conventional treatment after neoadjuvant chemotherapy, with 5-year OS rates of 62.5% and 61%, respectively.

Key prognostic factors for overall survival included the clinical T-stage before chemotherapy and the number of tumor-positive axillary lymph nodes after induction chemotherapy, highlighting their importance in predicting patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of high-dose chemotherapy and hematopoietic progenitor-cell support in operable breast cancer with extensive lymph node involvement: final analysis with 7 years of follow-up. Schrama, JG., Faneyte, IF., Schornagel, JH., et al.[2020]

In a study of 662 male and 150 female patients with stage IIIa non-small cell lung cancer (NSCLC), combined therapy (surgery plus chemotherapy and/or radiotherapy) resulted in a significantly higher 5-year survival rate of 23.5% compared to 16.4% for those who only underwent surgical resection.

The effectiveness of combined therapy varied by cancer type, with a 5-year survival rate of 27.6% for squamous cell carcinoma (SCC) and 23.5% for adenocarcinoma (AC), indicating that treatment strategies should consider TNM staging and cancer pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined therapy for stage IIIa non-small cell lung cancer]. Zhao, LQ., Hou, SC., Li, H., et al.[2005]

In a study of 155 patients with advanced solid tumors, those with a better performance status (ECOG PS 0-1) had a median overall survival (OS) of 9.1 months, compared to only 2.9 months for those with poorer performance status (ECOG PS 2-4), indicating that performance status significantly impacts treatment outcomes with immune checkpoint inhibitors (ICIs).

Despite having a poor performance status, 27.3% of patients in the study were still alive after one year, and the treatment was generally well-tolerated, with 84.6% of patients experiencing no severe toxicities, suggesting that ICIs can be a safe and effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. Kapoor, A., Noronha, V., Patil, VM., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Disease-free survival as an end-point in the treatment of solid tumours--perspectives from clinical trials and clinical practice. [2014]

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

Trends in phase III randomized controlled clinical trials on the treatment of advanced non-small-cell lung cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Randomized trial of high-dose chemotherapy and hematopoietic progenitor-cell support in operable breast cancer with extensive lymph node involvement: final analysis with 7 years of follow-up. [2020]

4. China pubmed.ncbi.nlm.nih.gov

[Combined therapy for stage IIIa non-small cell lung cancer]. [2005]

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

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. [2023]