A study to test if different doses of D3S-001 used on its own or in combination with other anti-cancer medicines is safe and tolerable in people with advanced solid tumours with KRAS p.G12C modification

Overview

Sponsor-declared trial summary

Key facts

Sponsor

D3 Bio (Wuxi) Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Nov 2024 → ongoing

Decision date (initial)

2024-04-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

D3 Bio (Wuxi) Co. Ltd.

External identifiers

EU CT number

2023-508517-16-00

WHO UTN

U1111-1298-9680

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic, Others, Efficacy

Evaluate the safety and tolerability of D3S-001 as monotherapy (Part 1, Part 2 and Part 4a) and as combination therapy (Part 3) in adult subjects with KRAS p.G12C mutant solid tumors. Determine the MTD, if applicable, and the RP2D.

Secondary objectives 3

1. Characterize the PK of D3S-001 as monotherapy (Part 1, Part 2 and Part 4a) and as combination therapy (Part 3) following administration as an oral capsule formulation
2. Evaluate the effect of food on the oral PK of D3S-001 as monotherapy
3. Evaluate tumor response assessed by RECIST v1.1 of D3S-001 as monotherapy and combination therapy in advanced solid tumors with a KRAS p.G12C mutation

Conditions and MedDRA coding

Advanced Solid Tumors with a KRAS p.G12C Mutation

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Subject must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor which is progressing.
2. Subject must have documented KRAS p.G12C mutation identified within the last 5 years by a local test on tumor tissue or blood. (Note: For subjects with unknown KRAS mutation status, central laboratory testing on tumor tissue can be offered if available in respective region or country).Local KRAS p.G12C testing must be performed using a verified and well-validated test in line with local regulations, performed at a Clinical Laboratory Improvement Amendments certified or a College of American Pathologists accredited laboratory for the United States sites. An equivalent accredited laboratory or following local clinical practice is required for sites outside the US United States and local testing methods must clearly identify KRAS p.G12C mutations distinctively from other KRAS mutations. Note: For subjects in Part 3a, subjects should have known PD-L1 expression per Dako 22C3, or willing to provide tissue samples for central testing. For all parts, if not specified, subjects should have no known second KRAS driver mutations (including G12A, G12V, G12R, G13C, G12D, G12S, H95, Y96, Q61, and R68).
3. Subjects must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as defined by at least 1 lesion that can be accurately measured at baseline as ≥10 mm at the longest diameter with computed tomography (CT) or magnetic resonance imaging (MRI) (except lymph nodes which must have a short axis ≥15 mm on CT), which is suitable for accurate, repeated measurements. Previously irradiated lesions or a lesion in the field of radiation should not be used as measurable disease unless the lesion(s) has/have demonstrated unequivocal disease progression by RECIST v1.1. Target lesions should not be used for the baseline tumor biopsy, unless there are no other lesions suitable for biopsy and they fulfil requirements outlined in the study protocol.
4. Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Subjects must have adequate organ and marrow function within the screening period as defined in the study protocol.

Exclusion criteria 5

1. Subject has any prior treatment without adequate washout periods as defined in the study protocol.
2. 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.
3. Subject has unresolved treatment-related toxicities from previous anti-cancer therapy of NCI CTCAE Grade ≥2 (with exception of vitiligo or alopecia). a. The following criteria will be only applied to KRAS p.G12Ci-pretreated subjects. The subjects will be ineligible if any 1 of the following criterion was met in the prior KRAS p.G12Ci treatment period: i. Grade 3 or higher ALT and/or AST increased at >2 occurrences ii. Grade 3 or higher cardiac toxicity (ECG QT corrected interval prolonged and ejection fraction decreased) Note: Subjects with other chronic Grade 2 toxicities (e.g., Grade 2 chemotherapy-induced neuropathy) may be eligible per discretion of the Investigator after consultation with the Medical Monitor. Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment may be included only after consultation with the medical Monitor.
4. Subject has active gastrointestinal disease or other condition (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, malabsorption syndrome, or previous significant bowel resection) that could interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g., that would preclude adequate absorption of D3S-001.)
5. Concurrent participation in any clinical research study involving treatment with any investigational drug, radiotherapy, or surgery, except for the non-treatment phases of these studies (e.g., follow-up phase).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Treatment-emergent AEs, treatment-related Aes
2. Clinically significant changes in vital signs, physical examinations, ECGs, and clinical laboratory test
3. The MTD, if applicable, will be based on DLTs
4. The RP2D in the expansion part will be based on emerging data

Secondary endpoints 3

1. PK parameters of D3S-001 including, but not limited to: Cmax, tmax, t1/2, and AUC
2. PK parameters of D3S-001 including, but not limited to: Cmax, tmax, t1/2, and AUC in the fed versus. fasted states for the food effect assessment
3. ORR, DOR, DCR, DCR at 24 weeks (CR, PR, or SD ≥24 weeks), and PFS as assessed per RECIST v1.1 by investigators and BICR

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

D3 Bio (Wuxi) Co. Ltd.

Sponsor organisation

D3 Bio (Wuxi) Co. Ltd.

Address

324 No 88 Meiliang Road, Mashan Street, Binhu District Mashan Street Binhu District

City

Wuxi

Postcode

214091

Country

China

Scientific contact point

Organisation

D3 Bio (Wuxi) Co. Ltd.

Contact name

Chase Chen

Public contact point

Organisation

D3 Bio (Wuxi) Co. Ltd.

Contact name

Amy Zhou

Third parties 5

Locations

4 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 48 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications