a Study to Evaluate the Safety and Efficacy of D-1553 Combined With IN10018 in KRAS G12C Mutant Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase 1b/II, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of D-1553 Combined With IN10018 in Subjects With Locally Advanced or Metastatic Solid Tumors With KRAS G12C Mutation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06166836
• Other study ID #: D1553-106/IN10018-602
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 12, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: December 2023
• Source: InxMed (Shanghai) Co., Ltd.
• Contact: Shu Fang
• Phone: 86-15933968623
• Email: shu.fang[@]inxmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 1b/II, open-label study to evaluate the safety, tolerability, pharmacokinetics and antitumor activities of D-1553 in combination with IN10018 in subjects with locally advanced or metastatic solid tumor with KRAS G12C mutation.

Description:

This study includes 2 phases: Phase Ib-Dose Escalation and Phase II-Dose Expansion. Phase Ib-Dose Escalation part will enroll at least 6 subjects to identify the safety and RP2D of D1553 in combination with IN10018 in KRAS G12C mutant solid tumors. Phase II-Dose Expansion part contains 3 cohorts with cohort A to enroll advanced colorectal cancer (CRC) with KRAS G12C mutation, cohort B to enroll advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation, and cohort C to enroll other advanced solid tumors with KRAS G12C mutation. Phase II study is to evaluate the safety and antitumor activities of D-1553 in combination with IN10018 in KRAS G12C mutant solid tumors. The sample size in each cohort is estimated per Simon's 2-stage design. In Cohort A, when Simon's 2-stage study achieved statistical hypothesis, an open-label, randomized study will be conducted for factorial analysis to evaluate the contribution of IN10018 in the combination regimen.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Men or women aged = 18 years at the time of signing the informed consent form.

2. Subjects with pathologically confirmed locally advanced or metastatic solid tumors.

3. Confirmed positive KRAS G12C mutation in tumor tissue or other biospecimens (only for phase1b) containing cancer cells or DNA.

4. Tumor types in different phases and cohorts: 1) Phase 1b: subjects with locally advanced or metastatic solid tumors who have progressed on or failed in standard therapy, and no standard treatment is available. 2) Phase II Cohort A: subjects with locally advanced or metastatic CRC. 3) Phase II Cohort B: subjects with locally advanced or metastatic NSCLC. 4) Phase 2 Cohort C: subjects with other locally advanced or metastatic solid tumors.

5. Has measurable lesions at baseline according to RECIST 1.1 criteria.

6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

7. Adequate bone marrow, liver, renal, and coagulation function within 7 days prior to the first dose.

Exclusion Criteria:

1. Prior KRAS G12C inhibitors treatment.

2. Have known symptoms of spinal cord compression, instable or symptomatic central nervous system (CNS) metastases, and/or carcinomatous meningitis.

3. Have a history of stroke or other serious cerebrovascular diseases within 12 months prior to the first dose.

4. Have had interstitial lung disease or any active infection requiring systemic treatment within 14 days prior to the first dose.

5. Has a history of severe cardiovascular disease such as acute myocardial infarction, severe/unstable angina, QTc prolongation, or poorly controlled hypertension.

6. Haven't recovered from toxicity due to prior antitumor therapy

7. Pregnant or lactating women.

8. Malignant neoplasms other than study disease within 5 years prior to enrollment.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• D1553
D1553 orally taken,600mg twice a day
• IN10018(Ifebemtinib)
IN10018 orally taken once daily at approximately the same time each day

Locations

Country	Name	City	State
China	First Affiliated Hospital of Bengbu Medical College	Bengbu
China	Hunan Cancer Hospital	Changsha
China	Fujian Cancer Hospital	Fuzhou
China	First Affiliated Hospital of Gannan Medical University	Ganzhou
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	General Hospital Of Eastern Theater Command	Nanjing
China	Renmin Hospital of Wuhan University	Wuhan
China	Xuzhou Central Hospital	Xuzhou
China	Henan Cancer Hospital	Zhengzhou
China	The first Affiliated Hospital of Zhengzhou University	Zhengzhou

Sponsors (2)

Lead Sponsor	Collaborator
InxMed (Shanghai) Co., Ltd.	InventisBio Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended phase II dose (RP2D) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation	Evaluate the number of patients with dose-limited toxicities (DLTs); Determine the RP2D of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation.	Through study completion, approximately 3 years
Primary	Objective Response Rate (ORR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation	Defined as the proportion of subjects with complete response (CR) or partial response (PR).	Through study completion, approximately 3 years
Secondary	Progression-free Survival (PFS) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation	Defined as the time from the first dose of study treatment to first documentation of disease progression or to death due to any cause, whichever comes first.	Through study completion, approximately 3 years
Secondary	Duration of Response (DoR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation	Defined as the time from start of the first documentation of CR or PR to the first documentation of disease progression or to death due to any cause, whichever comes first.	Through study completion, approximately 3 years
Secondary	Disease Control Rate (DCR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation	Defined as the proportion of patients with CR, PR, or stable disease (SD).	Through study completion, approximately 3 years
Secondary	Overall survival (OS) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation	Defined as the time from the first dose of study treatment to the date of death due to any cause.	Through study completion, approximately 3 years
Secondary	Number of subjects with adverse event	The number of subjects who experienced AEs is presented.	Through study completion, approximately 3 years
Secondary	Plasma concentrations of D-1553 and IN10018 in solid tumors with KRAS G12C mutation	Plasma concentrations of D-1553 and IN10018	Through study completion, approximately 3 years
Secondary	PK: Cmax of D-1553 and IN10018	Maximum concentration (Cmax)	Through study completion, approximately 3 years
Secondary	PK: Cmin of D-1553 and IN10018	Minimum concentration (Cmin)	Through study completion, approximately 3 years
Secondary	PK:t1/2 of D-1553 and IN10018	Elimination half-life (t1/2).	Through study completion, approximately 3 years
Secondary	PK:CL/F of D-1553 and IN10018	apparent clearance (CL/F)	Through study completion, approximately 3 years
Secondary	PK:Vd/F of D-1553 and IN10018	Apparent volume of distribution (Vd/F)	Through study completion, approximately 3 years
Secondary	PK: AUC of D-1553 and IN10018	Area under the concentration-time curve (AUC)	Through study completion, approximately 3 years