JYP0322 Versus Platinum Based Doublet Chemotherapy in ROS1 Positive Patients Previously Treated With ROS1-TKIs.

Official title

A Randomized, Open-Label, Multicenter, Phase 3 Study Evaluating the Efficacy and Safety of JYP0322 Versus Platinum-Based Chemotherapy in ROS1-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer Patients Previously Treated With ROS1-TKI Therapy.

Overview

The primary purpose of the study was to compare progression-free survival of JYP0322 vs. platinum-based doublet chemotherapy in patients previously treated with ROS1-TKIs. Patients in the chemotherapy arm are given the option to switch to JYP0322 after BICR confirmed progressive disease (PD), while also have the choice to pursue with other drugs after discussing with their physicians.

Detailed description

This is a phase III, open label, randomized study assessing JYP0322 (150 mg, orally, tid) versus platinum-based doublet chemotherapy in subjects with confirmed diagnosis of ROS1 fusion positive NSCLC, who have progressed following prior therapy with one or two approved ROS1 Tyrosine Kinase Inhibitor (ROS1-TKI) agents and whose tumors harbors a ROS1 fusion positive. Subjects must agree to provide a biopsy for central confirmation of ROS1 fusion status. A total of 207 patients will be randomly assigned in a 2:1 ratio to receive oral JYP0322 (at a dose of 150mg tid) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus carboplatin (target area under the curve 5 \[AUC5\]) every 3 weeks for up to six cycles. Patients without disease progression after four cycles of platinu

Interventions

• Drug Pemetrexed injection
  Randomization to either JYP0322 or platinum-based doublet-chemotherapy on Day 1 of every 21d cycle in a 2:1 (JYP0322: platinum-based doublet-chemotherapy) ratio
• Drug Cross-over to JYP0322
  Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by BICR, they will be given the opportunity to begin treatment with JYP0322 150mg tid. These subjects may continue treatment with JYP0322 if they are continuing to show clinical benefit until disease progression as judged by the investigator.
• Drug JYP0322 tablets
  JYP0322, 150 mg, administered orally three times daily (tid) after meals; sample size (N) = 60.

Primary outcome measures

• Progression Free Survival (PFS) by BICR Assessment [Time frame: UP to 3 years]

Secondary outcome measures (6)

• Progression Free Survival (PFS) by investigators Assessment [Time frame: UP to 3 years]
• Overall Survival (OS) [Time frame: UP to 5 years]
• Objective Response Rate (ORR) by Investigator and BICR assessment [Time frame: RECIST tumor assessments every 6 weeks from randomization up to 3 years.]
• Duration of Response (DOR) by Investigator and BICR assessment [Time frame: RECIST tumor assessments every 6 weeks from randomization up to 3 years.]
• Disease Control Rate (DCR) by Investigator and BICR assessment [Time frame: RECIST tumor assessments every 6 weeks from randomization up to 3 years.]
• Time to Response (TTR) by Investigator and BICR assessment [Time frame: RECIST tumor assessments every 6 weeks from randomization up to 3 years.]

Eligibility criteria

Inclusion criteria

• Key Inclusion Criteria

• Subjects with histologically or cytologically documented NSCLC.
• Locally advanced or metastatic ROS1 fusion positive NSCLC.
• Prior one or two ROS1-TKI(s) Treatment.
• World Health Organization (WHO) performance status 0-1.
• Life expectancy of at least 3 months.
• At least one measurable lesion according to RECISIT 1.1.

Exclusion criteria

• Key Exclusion Criteria:

• Current participation in another therapeutic clinical trial.
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
• A history of severe allergies, or a history of severe allergy, hypersensitivity or other hypersensitivity to any active or inactive ingredient of the study drug.
• All acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade more than 1.
• Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
• Known active infe

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07154368 · JYP0322M302

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗