Clinical trial NCT05886920: Study of D3S-002 as Monotherapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations
Official title: A Phase 1, Open-label, Dose-escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Recommended Phase 2 Dose of D3S-002 Monotherapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors With MAPK Pathway Mutations
Keywords: Advanced solid tumors
mitogen-activated protein kinase
mutation
Lead sponsor: D3 Bio (Wuxi) Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-06-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion:

* Subjects must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor with evidence of progressive disease.
* 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).
* Subjects must be refractory to or intolerable with standard treatment, or have no available standard of care.
* 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.

Exclusion:

* Subject has any prior treatment with other treatments without adequate washout periods as defined in the protocol.
* 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.
* 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: First dose until 30 days after the last dose (or specified in the protocol)
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: From Cycle 1 Day 1 through Day 21. Each cycle is 21 days.
Secondary outcomes:
measure: D3S-002 maximum observed plasma concentration (Cmax)
timeFrame: First dose up to 24 months
measure: D3S-002 time to maximum plasma concentration (tmax)
timeFrame: First dose up to 24 months
measure: D3S-002 half-life (t1/2)
timeFrame: First dose up to 24 months
measure: D3S-002 area under the concentration-time curve (AUC)
timeFrame: First dose up to 24 months
measure: Objective response rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: Until disease progression or end of treatment (up to approximately 24 months)
measure: Disease control rate (DCR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: Until disease progression or end of treatment (up to approximately 24 months)
measure: Progression-free survival (PFS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: Until disease progression or end of treatment (up to approximately 24 months)
Other outcomes:
Locations:
city: Detroit
country: United States
facility: D3 Bio Investigative Site
state: Michigan
city: New York
country: United States
facility: D3 Bio Investigative Site
state: New York
city: Blacktown
country: Australia
facility: D3 Bio Investigative Site
state: New South Wales
city: Bedford Park
country: Australia
facility: D3 Bio Investigative Site
state: South Australia
city: Nedlands
country: Australia
facility: D3 Bio Investigative Site
state: Western Australia
city: Beijing
country: China
facility: D3 Bio Investigative Site
state: Beijing
city: Guangzhou
country: China
facility: D3 Bio Investigative Site
state: Guangdong
city: Harbin
country: China
facility: D3 Bio Investigative Site
state: Heilong Jiang
city: Shanghai
country: China
facility: D3 Bio Investigative Site
state: Shanghai
city: Hangzhou
country: China
facility: D3 Bio Investigative Site
state: Zhejiang
Study officials:
References: