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

Colorectal Cancer Clinical Trial

Official title:

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of QLC1101 Monotherapy in the Treatment of Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06403735
• Other study ID #: QLC1101-101
• Status: Recruiting
• Phase: Phase 1
• Start date: April 25, 2024
• Est. completion date: April 30, 2027

Study information

• Verified date: April 2024
• Source: Qilu Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: April 30, 2027
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Non-small Cell Lung Cancer
• Pancreatic Cancer
• Solid Tumor

Intervention

Drug:
• QLC1101
QLC1101 is an innovative small molecule inhibitor targeting KRAS G12D with independent intellectual property rights developed by Qilu Pharmaceutical Co., Ltd.QLC1101 can prevent GTP/GDP nucleotide exchange and/or the formation of KRAS G12D/GTP/RAF1 complex and inhibit mutant KRAS-dependent signal transduction by specifically binding to the KRAS G12D target, thereby inhibiting the generation of KRAS G12D mutant tumors.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong
China	Harbin Medical university cancer hospital	Ha'erbin	Heilongjiang
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	Shanghai east hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Qilu Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity (DLT)	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.	25 days after the first dose
Primary	MTD (or MAD)	the maximum tolerated dose (MTD) or maximum administered dose (MAD, if MTD fails to be determined) of QLC1101 monotherapy	1 year
Primary	RP2D	the recommended phase II dose of QLC1101 monotherapy	1.5 years
Secondary	Preliminary efficacy endpoints	Objective response rate (ORR)	3 years
Secondary	Preliminary efficacy endpoints	overall survival (OS)	3 years