Clinical trial NCT05410145: A Study of D3S 001 Monotherapy or Combination Therapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation
Official title: A Phase 1/2, Open Label, Dose-escalation, and Dose-expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of D3S 001 Monotherapy or Combination Therapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: KRAS P.G12C
Keywords: KRAS p.G12C
Mutation
advanced solid tumors
Lead sponsor: D3 Bio (Wuxi) Co., Ltd
Sponsor class: INDUSTRY
First posted: 2022-06-08
Enrollment: 442
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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, pharmacokinetics, pharmacodynamics, and preliminary efficacy of D3S-001 or combination therapy in subjects with advanced KRAS p.G12C mutant solid tumors. D3S-001 will be taken daily by oral administration in 21-day treatment cycles.


Eligibility criteria: Inclusion:

* Subject must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor which is progressing.
* Subject must have documented KRAS p.G12C mutation identified within the last 5 years by a local test on tumor tissue or blood.
* Subject must have measurable disease per RECIST v1.1.
* Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 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.
* Concurrent participation in any clinical research study involving treatment with any investigational drug, radiotherapy, or surgery, except for the nontreatment phases of these studies (e.g., follow-up phase).

Other protocol inclusion/exclusion criteria may apply

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From 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-001 maximum observed plasma concentration (Cmax)
timeFrame: Up to 24 months.
measure: D3S-001 time to maximum plasma concentration (tmax)
timeFrame: Up to 24 months.
measure: D3S-001 half-life (t1/2)
timeFrame: Up to 24 months.
measure: D3S-001 area under the concentration-time curve (AUC)
timeFrame: 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: Up to 24 months.
measure: Duration of Response (DOR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: Up to 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: Up to 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: Up to 24 months.
Other outcomes:
Locations:
city: Orange
country: United States
facility: D3 Bio Investigative Site
state: California
city: Denver
country: United States
facility: D3 Bio Investigative Site
state: Colorado
city: Sarasota
country: United States
facility: D3 Bio Investigative Site
state: Florida
city: Detroit
country: United States
facility: D3 Bio Investigative Site
state: Michigan
city: Nashville
country: United States
facility: D3 Bio Investigative Site
state: Tennessee
city: Houston
country: United States
facility: D3 Bio Investigative Site
state: Texas
city: Sydney
country: Australia
facility: D3 Bio Investigative Site
state: New South Wales
city: Malvern
country: Australia
facility: D3 Bio Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: D3 Bio Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: D3 Bio Investigative Site
state: Western Australia
city: Bedford Park
country: Australia
facility: D3 Bio Investigative Site
city: Beijing
country: China
facility: D3 Bio Investigative Site
state: Beijing
city: Guangzhou
country: China
facility: D3 Bio Investigative Site
state: Guangdong
city: Hangzhou
country: China
facility: D3 Bio Investigative Site
state: Hangzhou
city: Harbin
country: China
facility: D3 Bio Investigative Site
state: Heilongjiang
city: Wuhan
country: China
facility: D3 Bio Investigative Site
state: Hubei
city: Wuhan
country: China
facility: D3 Bio Investigative Site
state: Hubei
city: Nanchang
country: China
facility: D3 Bio Investigative Site
state: Jiangxi
city: Shenyang
country: China
facility: D3 Bio Investigative Site
state: Liaoning
city: Jinan
country: China
facility: D3 Bio Investigative Site
state: Shandong
city: Shanghai
country: China
facility: D3 Bio Investigative Site
state: Shanghai
city: Shanghai
country: China
facility: D3 Bio Investigative Site
state: Shanghai
city: Chengdu
country: China
facility: D3 Bio Investigative Site
state: Sichuan
city: Hangzhou
country: China
facility: D3 Bio Investigative Site
state: Zhejiang
city: Changsha
country: China
facility: D3 Bio Investigative Site
city: Hefei
country: China
facility: D3 Bio Investigative Site
city: Zhengzhou
country: China
facility: D3 Bio Investigative Site
city: Bordeaux
country: France
facility: D3 Bio Investigative Site
city: Lyon
country: France
facility: D3 Bio Investigative Site
city: Rennes
country: France
facility: D3 Bio Investigative Site
city: Villejuif
country: France
facility: D3 Bio Investigative Site
city: Hamburg
country: Germany
facility: D3 Bio Investigative Site
city: Sha Tin
country: Hong Kong
facility: D3 Bio Investigative Site
city: Candiolo
country: Italy
facility: D3 Bio Investigative Site
city: Milano
country: Italy
facility: D3 Bio Investigative Site
city: Napoli
country: Italy
facility: D3 Bio Investigative Site
city: Rome
country: Italy
facility: D3 Bio Investigative Site
city: Cheongju-si
country: Korea, Republic of
facility: D3 Bio Investigative Site
state: North Chungcheong
city: Seoul
country: Korea, Republic of
facility: D3 Bio Investigative Site
city: Seoul
country: Korea, Republic of
facility: D3 Bio Investigative Site
city: Seoul
country: Korea, Republic of
facility: D3 Bio Investigative Site
city: Barcelona
country: Spain
facility: D3 Bio Investigative Site
city: Madrid
country: Spain
facility: D3 Bio Investigative Site
city: Madrid
country: Spain
facility: D3 Bio Investigative Site
city: Valencia
country: Spain
facility: D3 Bio Investigative Site
city: Valencia
country: Spain
facility: D3 Bio Investigative Site
Study officials:
affiliation: D3 Bio (Wuxi) Co., Ltd
name: Cheng Chen, MD
role: STUDY_DIRECTOR
References: