Advanced Solid Tumors With MAPK Pathway MutationsPhase 1/2NCT05886920
A Phase 1/2 Study of D3S-002 as Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations
A Phase 1/2 study testing D3S-002 and D3S-001 in people with Advanced Solid Tumors With MAPK Pathway Mutations, run by D3 Bio (Wuxi) Co., Ltd at 18 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors With MAPK Pathway Mutations
- What is being tested?
- D3S-002 and D3S-001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 18 sitesin 4 countries
- Study dates
- 10 Jul 2023to Aug 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Part 1: Subjects must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor with evidence of progressive disease.
- Part 2: Subjects must have a histologically or cytologically confirmed metastatic or locally advanced non-small cell lung cancer with evidence of PD.
- Subjects with non-small cell lung cancer (NSCLC) should have no known epidermal growth factor receptor (EGFR) mutations, ALK/ROS1/RET rearrangements, NTRK1/2/3 gene fusions, v-Raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutations, or MET exon 14 skipping mutations.
- Note: EGFR mutations include but are not limited to EGFR Exon19 Deletions, Exon21 p.L858R, Exon21 p.L861Q, Exon18 p.G719X, Exon20 p.S768I, Exon20 Insertions, Exon20 p.T790M. If other EGFR mutations are present, the Investigator should have a consultation with the sponsor's Medical Monitor before making the enrollment decision.
- Part1: Subjects must have documented mitogen-activated protein kinase (MAPK) pathway mutation(s) within the last 5 years identified by a local test on tumor tissue or blood (eg, rat sarcoma (RAS), rapidly accelerated fibrosarcoma (RAF), and MAPK kinase (MAPKK) mutations).
- Part 2: Subject must have documented Kirsten rat sarcoma viral oncogene (KRAS) p. glycine 12 to cysteine (p.G12C) mutation identified within the last 5 years by a local test on tumor tissue or blood.
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- Note:
- All the local tests should clearly distinguish KRAS p.G12C from all other KRAS p.G12x variants. If not specified, subjects should have no known second KRAS mutations (including G12A, G12V, G12R, G13C, G12D, G12S, H95, Y96, Q61, and R68).
- Part 1: Subjects must be refractory to or intolerable with standard treatment, or have no available standard of care (SOC).
- Part 2: Subject must have received at least 1 line of prior standard of care systemic therapy for locally advanced and unresectable or metastatic disease, including KRAS p.G12C inhibitor.
- Note:
- Subjects should only have received 1 type of prior KRAS p.G12Ci treatment (including all types of KRAS p.G12C inhibitor which are either under investigation or in market, except D3S-001).
- During the prior KRAS p.G12C treatment, subject has achieved best response of partial or complete response regardless of KRAS p.G12Ci treatment duration, or stable disease for at least 6 months. However, subjects, who have stopped KRAS p.G12Ci therapy earlier than 6 months due to safety/tolerability reasons only, would be allowed. In such a situation, the Investigator should have a consultation with the Sponsor Medical Monitor before making the enrollment decision.
- Part 2: Subjects must have measurable disease per RECIST v1.1.
- Part 2: Subjects must agree to provide archival tumor tissue, if available, for genetic analysis. If archival tumor tissue is not available, or of insufficient quantity, an optional fresh biopsy is highly recommended.
- Part 2: Subjects must agree to provide blood samples for genetic analysis (Table 2 schedule of activities for Part 2).
- Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Subject must have adequate organ and marrow function within the screening period.
- Subjects must comply with all reproductive and contraceptive requirements outlined in the protocol.
Who cannot join
- Subject has any prior treatment with other treatments without adequate washout periods as defined in the protocol.
- Part 2: subjects with mixed small-cell lung cancer, or large cell neuroendocrine histology, or sarcomatoid carcinoma.
- Subject has uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the subject to give written informed consent.
- Part 1: Uncontrolled or untreated brain metastasis.
- Part 2: Asymptomatic and stable brain metastases subjects will be eligible for enrollment per the following criteria.
- Treated or untreated brain metastases
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- Neurologically asymptomatic
- Stable and not requiring steroids more than 10 mg/day of prednisone or equivalent for at least 4 weeks prior to the first dose of study medication.
- Subject has unresolved treatment-related toxicities from previous anticancer therapy of NCI CTCAE Grade ≥2 (with exception of vitiligo or alopecia).
- Subject has active gastrointestinal disease or other that could interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy.
- Any concurrent chemotherapy, immunotherapy, targeted therapy, cell therapy, biologic or hormonal therapy and any medical devices for cancer treatment.
- NOTE: Other protocol inclusion/exclusion criteria may apply
Trial locations and contacts
18 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
18 sites in 4 countries
China8 sites, 6 recruiting
- Recruiting
D3 Bio Investigative Site
Beijing, Beijing Municipality, 100142
- Recruiting
D3 Bio Investigative Site
Chengdu, Sichuan, 610041
- Recruiting
D3 Bio Investigative Site
Guangzhou, Guangdong, 510080
- Recruiting
D3 Bio Investigative Site
Hangzhou, Zhejiang, 310009
- Suspended
D3 Bio Investigative Site
Harbin, Heilong Jiang, 150081
- Recruiting
D3 Bio Investigative Site
Shanghai, Shanghai Municipality, 200030
- Active, not recruiting
D3 Bio Investigative Site
Shanghai, Shanghai Municipality, 201801
- Recruiting
D3 Bio Investigative Site
Wuhan, Hubei, 430079
Australia5 sites, 2 recruiting
- Completed
D3 Bio Investigative Site
Bedford Park, South Australia, 5042
- Completed
D3 Bio Investigative Site
Blacktown, New South Wales, 2148
- Recruiting
D3 Bio Investigative Site
Macquarie Park, New South Wales, 2109
- Recruiting
D3 Bio Investigative Site
Melbourne, Victoria, 3000
- Completed
D3 Bio Investigative Site
Nedlands, Western Australia, 6009
United States4 sites, 3 recruiting
- Recruiting
D3 Bio Investigative Site
Detroit, Michigan, 48202
- Recruiting
D3 Bio Investigative Site
Houston, Texas, 77030
- Recruiting
D3 Bio Investigative Site
Nashville, Tennessee, 37203
- Completed
D3 Bio Investigative Site
New York, New York, 10029
South Korea1 site, 1 recruiting
- Recruiting
D3 Bio Investigative Site
Seoul, 03722
About this study
Official title: A Phase 1/2, Open Label, Dose-escalation, and Dose-expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Recommended Phase 2 Dose of D3S-002 Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations
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.
- Being tested
- D3S-002, D3S-001
- Keywords
- Advanced solid tumors, mitogen-activated protein kinase, mutation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D3S-002Drug
Oral Tablet
D3S-001Drug
Oral Capsule
| Study group | Role | What they receive |
|---|---|---|
| D3S-002 Monotherapy | Experimental | Part 1: Dose Escalation, D3S-002 administered orally. Receives: Drug: D3S-002 |
| D3S-002 and D3S-001 Combination Therapy | Experimental | Part 2a: Dose Escalation, D3S-002 and D3S-001 administered orally.
Part 2b: Dose Expansion, D3S-002 and D3S-001 administered orally. Receives: Drug: D3S-002; Drug: D3S-001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs)
Measured: First dose until 30 days after the last dose (or specified in the protocol)
Maximum tolerated dose (MTD) based on Dose limiting toxicities (DLTs)
Measured: First dose up to 24 months
Recommended Phase 2 dose (RP2D)
Measured: First dose up to 24 months
Secondary outcomes (11)
Part 1: D3S-002 maximum observed plasma concentration (Cmax)
Measured: First dose up to 24 months
Part 2: D3S-002 and D3S-001 maximum observed plasma concentration (Cmax)
Measured: First dose up to 24 months
Part 1: D3S-002 time to maximum plasma concentration (tmax)
Measured: First dose up to 24 months
Part 2: D3S-002 and D3S-001 time to maximum plasma concentration (tmax)
Measured: First dose up to 24 months
Part 1: D3S-002 half-life (t1/2)
Measured: First dose up to 24 months
Part 2: D3S-002 and D3S-001 half-life (t1/2)
Measured: First dose up to 24 months
Part 1: D3S-002 area under the concentration-time curve (AUC)
Measured: First dose up to 24 months
Part 2: D3S-002 and D3S-001 area under the concentration-time curve (AUC)
Measured: First dose up to 24 months
Objective response rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Measured: Until disease progression or end of treatment (up to approximately 24 months)
Disease control rate (DCR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Measured: Until disease progression or end of treatment (up to approximately 24 months)
Progression-free survival (PFS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Measured: Until disease progression or end of treatment (up to approximately 24 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2023
- Study start10 Jul 2023
- Primary completionAug 2028 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid Tumors With MAPK Pathway MutationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 67 participants (estimated)
Sponsor and investigators
- Lead sponsor
- D3 Bio (Wuxi) Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05886920
- Sponsor's protocol ID
- D3S-002-100
- Status last verified
- Sep 2026
- First submitted
- 24 May 2023
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open Label, Dose-escalation, and Dose-expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Recommended Phase 2 Dose of D3S-002 Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations
- ClinicalTrials.gov ID
- NCT05886920
- Acronym / sponsor ID
- D3S-002-100
- Keywords
- Advanced solid tumors, mitogen-activated protein kinase, mutation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 67 participants (estimated)
- Lead sponsor
- D3 Bio (Wuxi) Co., LtdIndustry (pharma, biotech, devices)
- Study start
- 10 Jul 2023 (actual)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 2 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D3S-002 Monotherapy | Experimental | Drug: D3S-002Part 1: Dose Escalation, D3S-002 administered orally. |
| D3S-002 and D3S-001 Combination Therapy | Experimental | Drug: D3S-002, Drug: D3S-001Part 2a: Dose Escalation, D3S-002 and D3S-001 administered orally. Part 2b: Dose Expansion, D3S-002 and D3S-001 administered orally. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Part 1: Subjects must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor with evidence of progressive disease.
- Part 2: Subjects must have a histologically or cytologically confirmed metastatic or locally advanced non-small cell lung cancer with evidence of PD.
- Note: EGFR mutations include but are not limited to EGFR Exon19 Deletions, Exon21 p.L858R, Exon21 p.L861Q, Exon18 p.G719X, Exon20 p.S768I, Exon20 Insertions, Exon20 p.T790M. If other EGFR mutations are present, the Investigator should have a consultation with the sponsor's Medical Monitor before making the enrollment decision.
- Part1: Subjects must have documented mitogen-activated protein kinase (MAPK) pathway mutation(s) within the last 5 years identified by a local test on tumor tissue or blood (eg, rat sarcoma (RAS), rapidly accelerated fibrosarcoma (RAF), and MAPK kinase (MAPKK) mutations).
- Part 2: Subject must have documented Kirsten rat sarcoma viral oncogene (KRAS) p. glycine 12 to cysteine (p.G12C) mutation identified within the last 5 years by a local test on tumor tissue or blood.
Key exclusion criteria (12 listed)
- Subject has any prior treatment with other treatments without adequate washout periods as defined in the protocol.
- Part 2: subjects with mixed small-cell lung cancer, or large cell neuroendocrine histology, or sarcomatoid carcinoma.
- Subject has uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the subject to give written informed consent.
- Part 1: Uncontrolled or untreated brain metastasis.
- Part 2: Asymptomatic and stable brain metastases subjects will be eligible for enrollment per the following criteria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D3S-002Oral Tablet | Drug | D3S-002 Monotherapy, D3S-002 and D3S-001 Combination Therapy |
| D3S-001Oral Capsule | Drug | D3S-002 and D3S-001 Combination Therapy |
Primary outcome
Number of Participants With Adverse Events (AEs)
Time frame: First dose until 30 days after the last dose (or specified in the protocol)
Maximum tolerated dose (MTD) based on Dose limiting toxicities (DLTs)
Time frame: First dose up to 24 months
Recommended Phase 2 dose (RP2D)
Time frame: First dose up to 24 months
11 secondary outcomes
Part 1: D3S-002 maximum observed plasma concentration (Cmax)
Time frame: First dose up to 24 months
Part 2: D3S-002 and D3S-001 maximum observed plasma concentration (Cmax)
Time frame: First dose up to 24 months
Part 1: D3S-002 time to maximum plasma concentration (tmax)
Time frame: First dose up to 24 months
Part 2: D3S-002 and D3S-001 time to maximum plasma concentration (tmax)
Time frame: First dose up to 24 months
Part 1: D3S-002 half-life (t1/2)
Time frame: First dose up to 24 months
Part 2: D3S-002 and D3S-001 half-life (t1/2)
Time frame: First dose up to 24 months
Part 1: D3S-002 area under the concentration-time curve (AUC)
Time frame: First dose up to 24 months
Part 2: D3S-002 and D3S-001 area under the concentration-time curve (AUC)
Time frame: First dose up to 24 months
Objective response rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time frame: Until disease progression or end of treatment (up to approximately 24 months)
Disease control rate (DCR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time frame: Until disease progression or end of treatment (up to approximately 24 months)
Progression-free survival (PFS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time frame: Until disease progression or end of treatment (up to approximately 24 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Individual participant dataSharing planned: No
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Active, not recruitingPhase 2
Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Recurrent Ependymal Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
18 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing D3S-002 and D3S-001 in people with Advanced Solid Tumors With MAPK Pathway Mutations, run by D3 Bio (Wuxi) Co., Ltd at 18 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in China, Australia, United States, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Medical Director (+86 21 61635900, D3bio_CT@d3bio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) (time frame: First dose until 30 days after the last dose (or specified in the protocol)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.