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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Pancreatic Cancer; Solid Tumor; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: QLC1101

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510699
      • Not yet recruiting
      • The First Affiliated Hospital of Guangdong Pharmaceutical University
      • Contact: Xicheng Wang, Professor; Phone Number: 13902400598; Email: 13902400598@126.com
  • Heilongjiang
    • Ha'erbin, Heilongjiang, China, 150081
      • Not yet recruiting
      • Harbin Medical University Cancer Hospital
      • Contact: Yanqiao Zhang, Professor; Phone Number: 13845120210; Email: yanqiaozhanggcp@163.com
  • Jiangxi
    • Nanchang, Jiangxi, China, 330029
      • Not yet recruiting
      • Jiangxi Cancer Hospital
      • Contact: Shanxian Guo, Professor; Phone Number: 15270019607; Email: guoshanxian0830@126.com
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Shanghai East Hospital
      • Contact: Caicun Zhou, professor; Phone Number: 13301825532; Email: caicunzhoudr@163.com
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Not yet recruiting
      • Yunnan Cancer Hospital
      • Contact: Runxiang Yang, Professor; Phone Number: 13888876721; Email: 13888876721@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
MTD (or MAD)	the maximum tolerated dose (MTD) or maximum administered dose (MAD, if MTD fails to be determined) of QLC1101 monotherapy	1 year
RP2D	the recommended phase II dose of QLC1101 monotherapy	1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary efficacy endpoints	Objective response rate (ORR)	3 years
Preliminary efficacy endpoints	overall survival (OS)	3 years

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: May 5, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: QLC1101-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No