A Phase I Clinical Study of QLC1101 in Patients With Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Colorectal Cancer; Pancreatic Cancer; Non-small Cell Lung Cancer; Solid Tumor
• Interventions: Drug: QLC1101

• Registration Number: NCT06403735
• Lead Sponsor: Qilu Pharmaceutical Co., Ltd.

Brief Summary

QLC1101 is a selective reversible inhibitor of KRAS G12D, with the dosage form of capsules and administration route of oral administration. In the first-in-humans (FIH) study, the sponsor will explore the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of QLC1101 in subjects with advanced solid tumors harboring a KRAS G12D mutation. The FIH study includes dose escalation, PK expansion, and efficacy expansion.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-04
• Study First Submitted: 2024-04-10
• Study Start: 2024-04-25
• Study First Submitted QC: 2024-05-05
• Last Update Submitted: 2024-05-05
• Study First Posted: 2024-05-08
• Last Update Posted: 2024-05-08
• Primary Completion: 2026-05-31
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

1. Patients with histologically confirmed advanced (metastatic or unresectable) solid tumors harboring a KRAS G12D mutation. Sign the ICF.
2. Those who fail or are unable to tolerate standard treatment, lack standard treatment, or refuse to receive standard treatment;
3. Those who are able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormality that may alter absorption;
4. Subjects who have at least one measurable lesion documented by computed tomography (CT) and/or magnetic resonance imaging (MRI) as confirmed by the investigator per the RECIST v1.1 criteria.
5. ECOG PS score: 0 or 1;
6. Expected survival time ≥ 3 months;
7. Adequate organ function at screening:

Exclusion Criteria

1. Previously treated with inhibitors against KRAS G12D mutation;
2. The period of time prior to the first dose of investigational product should be at least 28 days from previous treatment or at least 5 half-lives
3. Known immediate or delayed hypersensitivity or idiosyncratic reaction to the ingredients of the preparation used in the trial;
4. Presence of other active malignant tumors in addition to primary tumors;
5. Presence of serious lung diseases at screening;
6. Clinically significant gastrointestinal disorders or other conditions that seriously interfere with drug absorption;
7. Severe hereditary or acquired hemorrhagic diathesis or coagulation disorders;
8. Complicated with clinically significant cardiovascular and cerebrovascular disorders;
9. History of allogeneic hematopoietic stem cell transplantation or organ transplantation (except corneal transplantation);
10. Presence of known mental disorders, epilepsy, dementia, or alcohol and drug abuse that may affect the compliance with study requirements;
11. the investigator determines that participation in the study is not in the best interest of the subject.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
QLC1101	QLC1101	patients with advanced solid tumors harboring a KRAS G12D mutation were administrated with QLC1101 orally in a total of 6 dose groups at 100,200,400,600,900, and 1200 mg BID

Primary Outcome Measures

Name	Time	Method
Dose limiting toxicity (DLT)	25 days after the first dose	Subjects in this phase will be treated with single oral administration of QLC1101, observed for 4 days, and if tolerant, treated with repeated oral administration of QLC1101 twice daily for 21 consecutive days. After completing the DLT observation (the 25 days after the first dose as the DLT observation period), the subject will continue to receive repeated-dose treatment of Cycle 2 and subsequent cycles.
RP2D	1.5 years	the recommended phase II dose of QLC1101 monotherapy
MTD (or MAD)	1 year	the maximum tolerated dose (MTD) or maximum administered dose (MAD, if MTD fails to be determined) of QLC1101 monotherapy

Secondary Outcome Measures

Name	Time	Method
Preliminary efficacy endpoints	3 years	overall survival (OS)

Trial Locations

Locations (5)

The First Affiliated Hospital of Guangdong Pharmaceutical University; 🇨🇳 Guangzhou, Guangdong, China

Harbin Medical university cancer hospital; 🇨🇳 Ha'erbin, Heilongjiang, China

Jiangxi Cancer Hospital; 🇨🇳 Nanchang, Jiangxi, China

Yunnan Cancer Hospital; 🇨🇳 Kunming, Yunnan, China

Shanghai east hospital; 🇨🇳 Shanghai, Shanghai, China