Study to Assess the Safety, Tolerability, and Efficacy of IDX-1197 in Combination With XELOX or Irinotecan in Patients With Advanced Gastric Cancer

Study Overview
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Brief Summary
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This is an open-label, Phase 1b study to evaluate the safety and tolerability of IDX-1197 and determine the MTD and RP2D in combination with XELOX or irinotecan in patients with advanced gastric cancer.

Official Title
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An Open-Label, International, Multicenter, Phase 1b Study to Assess the Safety, Tolerability, and Efficacy of IDX-1197 in Combination With XELOX (Capecitabine and Oxaliplatin) or Irinotecan in Patients With Advanced Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: IDX-1197+XELOX
* Drug: IDX-1197+Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 1, patients with treatment-naïve recurrent or advanced metastatic gastric cancer including gastroesophageal junction or upper part of the stomach. Group 2, patients with recurrent or advanced metastatic gastric cancer including gastroesophageal junction or upper part of the stomach, who were treated ≥2 times with palliative chemotherapy before screening. At least 1 evaluable lesion for the dose escalation part and at least 1 measurable lesion according to RECIST v1.1 for the dose expansion part. Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Exclusion Criteria: Symptomatic central nervous system or uncontrolled brain metastasis Carcinomatous meningitis or its history. For Group 1, patients who are HER 2 positive. Any other concurrent uncontrolled illness including, but not limited to, active or ongoing symptomatic infection requiring IV antibiotic treatment, uncontrolled diabetes, hepatic, renal, or respiratory illness. Severe or unstable angina, myocardial infarction or ischemia, symptomatic congestive heart failure, arterial or venous thromboembolism requiring coronary artery bypass graft or stent within the past 6 months or clinically significant cardiac dysrhythmia or New York Heart Association class II   IV heart disease within 6 months of randomization. Uncontrolled hypertension Immunocompromised patients, such as patients known to be serologically positive for HIV. Patients with known active Hepatitis B or C infection. Patients with known active or symptomatic pneumonitis, or history of non-infectious pneumonitis requiring steroids. Diagnosis of a myelodysplastic syndrome/acute myeloid leukemia or its suspicious characteristics. Any unresolved clinically significant Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 toxicity Resting ECG with measurable QTcF > 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome. Current use of a cytochrome P3A4 inhibitor or inducer and strong uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) inhibitors.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1<br> | Drug: IDX-1197+XELOX<br>* The dose levels will be escalated following a 3+3 dose escalation scheme.<br>|
| Other: Group 2<br> | Drug: IDX-1197+Irinotecan<br>* The dose levels will be escalated following a 3+3 dose escalation scheme.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) | To determine the MTD and RP2D of IDX-1197 when given in combination with XELOX or Irinotecan. This will be accomplished by the standard 3+3 dose escalation design. If 2 of the 3 to 6 patients in a particular dose level experience a DLT, the dose escalation should be stopped at this dose level, and the MTD will be determined. | through study completion (Up to 12 months) | 
| Dose Limiting Toxicities (DLTs) | Occurrence of DLTs | during the first 21-day cycle for Group 1 and through first 2 cycles (14 days each) for Group 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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1197, IDX-1197, venadaparib