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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: D1553; Drug: IN10018（Ifebemtinib）

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Shu Fang; Phone Number: 86-15933968623; Email: shu.fang@inxmed.com
• Study Contact Backup: Name: Lily Li; Phone Number: 86-13911551669; Email: lily.li@inxmed.com

Study Locations

• China
  • Bengbu, China
    • Recruiting
    • First Affiliated Hospital of Bengbu Medical College
    • Contact: Mulin Liu
  • Changsha, China
    • Recruiting
    • Hunan Cancer hospital
    • Contact: Yongzhong Luo
  • Fuzhou, China
    • Recruiting
    • Fujian cancer hospital
    • Contact: Rongbo Lin
  • Ganzhou, China
    • Recruiting
    • First Affiliated hospital of GANNAN Medical University
    • Contact: Huaqiu Shi
  • Nanjing, China
    • Recruiting
    • General Hospital of Eastern Theater Command
    • Contact: Tangfeng LV
  • Wuhan, China
    • Recruiting
    • Renmin Hospital of Wuhan University
    • Contact: Ximing Xu
  • Xuzhou, China
    • Recruiting
    • XuZhou Central Hospital
    • Contact: Yuan Yuan
  • Zhengzhou, China
    • Recruiting
    • Henan Cancer Hospital
    • Contact: Ying Liu
  • Zhengzhou, China
    • Recruiting
    • The First Affiliated hospital of Zhengzhou University
    • Contact: Xingya Li
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Zhengbo Song, MD
      • Contact: Yiping Zhang
      • Principal Investigator: Liming Zhu

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b-Dose Escalation Part; To evaluate the safety and Recommended Phase 2 dose (RP2D) of D-1553 in combination with IN10018 in previously-treated solid tumors.	Drug: D1553; D1553 orally taken，600mg twice a day; Drug: IN10018（Ifebemtinib）; IN10018 orally taken once daily at approximately the same time each day; Other Names: BI 853520
Experimental: Phase II Cohort A-previously-treated CRC with KRAS G12C mutation（Treatmnt Group）; To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in previously-treated CRCs with KRAS G12C mutation.	Drug: D1553; D1553 orally taken，600mg twice a day; Drug: IN10018（Ifebemtinib）; IN10018 orally taken once daily at approximately the same time each day; Other Names: BI 853520
Active Comparator: Phase II Cohort A-previously-treated CRC with KRAS G12C mutation (Control Group); To evaluate the safety and antitumor efficacy of D-1553 in previously-treated CRCs with KRAS G12C mutation.	Drug: D1553; D1553 orally taken，600mg twice a day
Experimental: Phase II Cohort B-treatment-naïve or previously-treated NSCLC with KRAS G12C mutation; To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in advanced NSCLCs with KRAS G12C mutation.	Drug: D1553; D1553 orally taken，600mg twice a day; Drug: IN10018（Ifebemtinib）; IN10018 orally taken once daily at approximately the same time each day; Other Names: BI 853520
Experimental: Phase II Cohort C-other previously-treated solid tumors with KRAS G12C mutation; To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in other solid tumors with KRAS G12C mutation	Drug: D1553; D1553 orally taken，600mg twice a day; Drug: IN10018（Ifebemtinib）; IN10018 orally taken once daily at approximately the same time each day; Other Names: BI 853520

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Number of subjects with adverse event	The number of subjects who experienced AEs is presented.	Through study completion, approximately 3 years
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
PK: Cmax of D-1553 and IN10018	Maximum concentration (Cmax)	Through study completion, approximately 3 years
PK: Cmin of D-1553 and IN10018	Minimum concentration (Cmin)	Through study completion, approximately 3 years
PK:t1/2 of D-1553 and IN10018	Elimination half-life (t1/2).	Through study completion, approximately 3 years
PK:CL/F of D-1553 and IN10018	apparent clearance (CL/F)	Through study completion, approximately 3 years
PK:Vd/F of D-1553 and IN10018	Apparent volume of distribution (Vd/F)	Through study completion, approximately 3 years
PK: AUC of D-1553 and IN10018	Area under the concentration-time curve (AUC)	Through study completion, approximately 3 years

Collaborators and Investigators

• Sponsor: InxMed (Shanghai) Co., Ltd.
• Collaborators: InventisBio Co., Ltd
• Investigators: Principal Investigator: Zhengbo Song, Study Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 4, 2023
• First Submitted That Met QC Criteria: December 4, 2023
• First Posted (Actual): December 12, 2023

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: D1553-106/IN10018-602

Drug and device information, study documents

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