D3S-002 for Advanced Solid Tumors

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, D3S-002, for individuals with advanced solid tumors that have specific genetic changes known as MAPK pathway mutations. The primary goal is to assess the drug's safety and tolerability and determine the optimal dose for future studies. It targets those whose cancer has progressed despite other treatments or who cannot undergo standard treatments. Eligible participants should have a worsening solid tumor and a specific genetic mutation confirmed within the last five years. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that D3S-002 is likely to be safe for humans?

A previous study tested D3S-002 to assess its safety for humans. This marks the first administration of the drug to humans, so safety information remains limited. The research is in its early stages, and not all safety details are known.

The trial aims to evaluate how well participants tolerate D3S-002. It is administered to adults with certain advanced solid tumors, specifically those with MAPK pathway mutations, which the drug targets. As an early study, it focuses on identifying side effects and understanding the drug's behavior in the body.

Although detailed safety data is limited, the study's progression suggests researchers consider it safe enough for further testing, indicating that any side effects may be manageable. Prospective participants should consult their doctors to fully understand the risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced solid tumors, which often include chemotherapy and immunotherapy, D3S-002 offers a novel approach by being administered orally, which could improve patient comfort and compliance. This treatment is unique because it involves a dose escalation strategy, potentially allowing for more precise and effective targeting of tumors with fewer side effects. Researchers are excited about D3S-002 as it might offer a new mechanism of action compared to existing therapies, which could lead to better outcomes for patients with challenging tumor types.

What evidence suggests that D3S-002 might be an effective treatment for advanced solid tumors?

Research has shown that D3S-002 could help treat advanced solid tumors with specific genetic changes. In early lab studies, combining D3S-002 with other treatments stopped tumor growth by more than 80% and extended patient survival. This suggests D3S-002 might slow down or shrink tumors. Additionally, related studies reported that 60% of patients experienced tumor shrinkage, and 30% showed noticeable improvement. These early results indicate that D3S-002 could be a promising treatment for these cancers. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/83/7_Supplement/5501/723743/Abstract-5501-Vertical-inhibition-of-the-MAPK

Vertical inhibition of the MAPK pathway with D3S-002, a ... Adding D3S-002 to D3S-001 or MRTX849 resulted in over 80% tumor growth inhibition and significantly prolonged survival, suggesting the ...

2. trialx.com trialx.com/clinical-trials/listings/244900/study-of-d3s-002-as-monotherapy-in-adult-subjects-with-advanced-solid-tumors-with-mapk-pathway-mutations/?&geo_lat=39.9041999&geo_lng=116.4073963&radius=10&place=Beijing&user_country=China

Study of D3S-002 as Monotherapy in Adult Subjects With ... This first-in-human (FIH) study aims to assess the safety, tolerability, pharmacokinetics, and recommended phase 2 dose (RP2D) of D3S-002 given ...

3. delta.larvol.com delta.larvol.com/NewsItem/NewsItemID/69b53d18-9a4a-4538-b6b6-c5b7e99f4bef/Study+of+D3S-002+as+Monotherapy+in+Adult+Subjects+With+Advanced+Solid+Tumors+With+MAPK+Pathway+Mutations

Study of D3S-002 as Monotherapy in Adult Subjects With ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05410145

NCT05410145 | A Study of D3S-001 Monotherapy or ... This is a first-in-human (FIH), multicenter, open-label, dose-escalation, and dose-expansion Phase 1/2 clinical trial to evaluate the safety, tolerability, ...

5. bioworld.com bioworld.com/articles/720001-aacr-2025-d3-bio-immvira-present-solid-tumor-brain-cancer-data

AACR 2025: D3 Bio, Immvira present solid tumor, brain ... In that cohort, 60% of patients experienced tumor shrinkage, 30% achieved partial responses, and 80% achieved DCR. In addition, 11 of 14 ctDNA- ...

6. d3bio.com d3bio.com/press-releases/d3-bio-announces-receiving-an-orphan-drug-designation-and-two-ind-clearances-from-fda-for-its-compounds-and-presentation-of-pipeline-data-at-upcoming-aacr-2023

D3 Bio Announces Receiving an Orphan Drug Designation ... The Company will present its pipeline research data of D3S-002 and D3L-001 in poster sessions at the upcoming AACR 2023 Annual Meeting, from ...

7. synapse.patsnap.com synapse.patsnap.com/drug/b01e673d23e845b68edf4f54ffbf6d42

D3S-002 - Drug Targets, Indications, Patents D3S-001 is currently in Phase II for non-small-cell lung cancer, colorectal cancer, and pancreatic cancer.The pipeline also includes the Phase I candidate D3S- ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02201-4/fulltext

615MO Phase I/II study of D3S-001, a second generation ... D3S-001 is a 2nd generation KRAS G12C inhibitor (G12Ci) with faster target engagement kinetics, depletes cellular active G12C at nanomolar levels, ...