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

NCT06166836 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: D1553-106/IN10018-602
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• Progression-free Survival (PFS) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation

  Through study completion, approximately 3 years

• Duration of Response (DoR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation

  Through study completion, approximately 3 years

• Disease Control Rate (DCR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation

  Through study completion, approximately 3 years

• Overall survival (OS) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation

  Through study completion, approximately 3 years

• Number of subjects with adverse event

  Through study completion, approximately 3 years

Study Arms (5)

Phase 1b-Dose Escalation Part

EXPERIMENTAL

To evaluate the safety and Recommended Phase 2 dose (RP2D) of D-1553 in combination with IN10018 in previously-treated solid tumors.

Drug: D1553; Drug: IN10018（Ifebemtinib）

Phase II Cohort A-previously-treated CRC with KRAS G12C mutation（Treatmnt Group）

EXPERIMENTAL

To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in previously-treated CRCs with KRAS G12C mutation.

Drug: D1553; Drug: IN10018（Ifebemtinib）

Phase II Cohort A-previously-treated CRC with KRAS G12C mutation (Control Group)

ACTIVE COMPARATOR

To evaluate the safety and antitumor efficacy of D-1553 in previously-treated CRCs with KRAS G12C mutation.

Drug: D1553

Phase II Cohort B-treatment-naïve or previously-treated NSCLC with KRAS G12C mutation

EXPERIMENTAL

To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in advanced NSCLCs with KRAS G12C mutation.

Drug: D1553; Drug: IN10018（Ifebemtinib）

Phase II Cohort C-other previously-treated solid tumors with KRAS G12C mutation

EXPERIMENTAL

To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in other solid tumors with KRAS G12C mutation

Drug: D1553; Drug: IN10018（Ifebemtinib）

Interventions

D1553 DRUG

D1553 orally taken，600mg twice a day

Phase 1b-Dose Escalation Part; Phase II Cohort A-previously-treated CRC with KRAS G12C mutation (Control Group); Phase II Cohort A-previously-treated CRC with KRAS G12C mutation（Treatmnt Group）; Phase II Cohort B-treatment-naïve or previously-treated NSCLC with KRAS G12C mutation; Phase II Cohort C-other previously-treated solid tumors with KRAS G12C mutation

IN10018（Ifebemtinib） DRUG

IN10018 orally taken once daily at approximately the same time each day

Also known as: BI 853520

Phase 1b-Dose Escalation Part; Phase II Cohort A-previously-treated CRC with KRAS G12C mutation（Treatmnt Group）; Phase II Cohort B-treatment-naïve or previously-treated NSCLC with KRAS G12C mutation; Phase II Cohort C-other previously-treated solid tumors with KRAS G12C mutation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women aged ≥ 18 years at the time of signing the informed consent form.
• Subjects with pathologically confirmed locally advanced or metastatic solid tumors.
• Confirmed positive KRAS G12C mutation in tumor tissue or other biospecimens (only for phase1b) containing cancer cells or DNA.
• 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.
• Has measurable lesions at baseline according to RECIST 1.1 criteria.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone marrow, liver, renal, and coagulation function within 7 days prior to the first dose.

You may not qualify if:

• Prior KRAS G12C inhibitors treatment.
• Have known symptoms of spinal cord compression, instable or symptomatic central nervous system (CNS) metastases, and/or carcinomatous meningitis.
• Have a history of stroke or other serious cerebrovascular diseases within 12 months prior to the first dose.
• Have had interstitial lung disease or any active infection requiring systemic treatment within 14 days prior to the first dose.
• Has a history of severe cardiovascular disease such as acute myocardial infarction, severe/unstable angina, QTc prolongation, or poorly controlled hypertension.
• Haven't recovered from toxicity due to prior antitumor therapy
• Pregnant or lactating women.
• Malignant neoplasms other than study disease within 5 years prior to enrollment.

Sponsors & Collaborators

• InxMed (Shanghai) Co., Ltd.: lead
• InventisBio Co., Ltd: collaborator

Study Sites (10)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310005, China

Location

First Affiliated Hospital of Bengbu Medical College

Bengbu, China

Location

Hunan Cancer Hospital

Changsha, China

Location

Fujian Cancer Hospital

Fuzhou, China

Location

First Affiliated Hospital of Gannan Medical University

Ganzhou, China

Location

General Hospital Of Eastern Theater Command

Nanjing, China

Location

Renmin Hospital of Wuhan University

Wuhan, China

Location

Xuzhou Central Hospital

Xuzhou, China

Location

Henan Cancer Hospital

Zhengzhou, China

Location

The first Affiliated Hospital of Zhengzhou University

Zhengzhou, China

Location

Study Officials

• Zhengbo Song

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2023
• First Posted: December 12, 2023
• Study Start: October 12, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 25, 2026

Record last verified: 2025-04

Locations

CN (10)