Clinical trial NCT06166836: a Study to Evaluate the Safety and Efficacy of D-1553 Combined With IN10018 in KRAS G12C Mutant Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Lead sponsor: InxMed (Shanghai) Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: InventisBio Co., Ltd
First posted: 2023-12-12
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recommended phase II dose (RP2D) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
timeFrame: Through study completion, approximately 3 years
measure: Objective Response Rate (ORR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
timeFrame: Through study completion, approximately 3 years
Secondary outcomes:
measure: Progression-free Survival (PFS) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
timeFrame: Through study completion, approximately 3 years
measure: Duration of Response (DoR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
timeFrame: Through study completion, approximately 3 years
measure: Disease Control Rate (DCR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
timeFrame: Through study completion, approximately 3 years
measure: Overall survival (OS) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
timeFrame: Through study completion, approximately 3 years
measure: Number of subjects with adverse event
timeFrame: Through study completion, approximately 3 years
measure: Plasma concentrations of D-1553 and IN10018 in solid tumors with KRAS G12C mutation
timeFrame: Through study completion, approximately 3 years
measure: PK: Cmax of D-1553 and IN10018
timeFrame: Through study completion, approximately 3 years
measure: PK: Cmin of D-1553 and IN10018
timeFrame: Through study completion, approximately 3 years
measure: PK:t1/2 of D-1553 and IN10018
timeFrame: Through study completion, approximately 3 years
measure: PK:CL/F of D-1553 and IN10018
timeFrame: Through study completion, approximately 3 years
measure: PK:Vd/F of D-1553 and IN10018
timeFrame: Through study completion, approximately 3 years
measure: PK: AUC of D-1553 and IN10018
timeFrame: Through study completion, approximately 3 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Bengbu
country: China
facility: First Affiliated Hospital of Bengbu Medical College
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Ganzhou
country: China
facility: First Affiliated Hospital of Gannan Medical University
city: Nanjing
country: China
facility: General Hospital Of Eastern Theater Command
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhengzhou
country: China
facility: The first Affiliated Hospital of Zhengzhou University
Study officials:
affiliation: Study Principal Investigator
name: Zhengbo Song
role: PRINCIPAL_INVESTIGATOR
References: