Ningetinib (CT053PTSA) Plus Gefitinib in Stage IIIB or IV NSCLC Patients With EGFR Mutation and T790M Negative

• ClinicalTrials.gov Identifier: NCT03758287
• Recruitment Status: Recruiting
• First Posted: November 29, 2018
• Last Update Posted: September 18, 2020
• Sponsor: Sunshine Lake Pharma Co., Ltd.
• Information provided by (Responsible Party): Sunshine Lake Pharma Co., Ltd.

Study Description

Brief Summary:

This is a phase Ib, multi-center, open label study evaluating the safety and efficacy of CT053PTSA in combination with gefitinib in patients with EGFR mutation, T790M negative NSCLC who have progressed after EGFR TKI treatment.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: CT053PTSA; Drug: Gefitinib	Phase 1; Phase 2

Detailed Description:

This study is being carried out in two parts, part 1 and part 2.

Part 1: This is the dose-escalation part. The primary purpose of the part 1 portion is to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and recommend the appropriate doses of CT053PTSA in combination with gefitinib for further studies.

Part 2: This is the expansion part. The part 2 portion of this study will continue to evaluate the safety and efficacy of the combination of CT053PTSA and gefitinib , at the appropriate doses recommended in Part 1, in patients with EGFR mutation, T790M negative NSCLC.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 158 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib, Multi-center, Open Label Study of Ningetinib (CT053PTSA) in Combination With Gefitinib in Stage IIIB or IV NSCLC Patients With EGFR Mutation and T790M Negative Who Have Progressed After EGFR TKI Therapy
• Actual Study Start Date: November 2016
• Estimated Primary Completion Date: August 17, 2021
• Estimated Study Completion Date: November 17, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: CT053PTSA +Gefitinib; Patients will receive CT053PTSA and gefitinib over a 28-day cycle until progressive disease, intolerable toxicity or subject's withdrawal from treatment. CT053PTSA will be administered daily, at a dose of 30 mg/40mg/60mg orally . Gefitinib will be administered daily, at a dose of 250 mg orally .	Drug: CT053PTSA; Other Name: Ningetinib; Drug: Gefitinib; Other Name: Iressa

Outcome Measures

Primary Outcome Measures :

1. Part 1（dose-escalation part）: Maximum Tolerated Dose (MTD) [ Time Frame: Cycle 1 Day 1 to Cycle 1 Day 28 ]
   The maximum tolerated dose (MTD) of the CT053PTSA and gefitinib combination will be determined according to incidence of dose-limiting toxicity (DLT) assessed by NCI CTCAE v4.03
2. Part 2（expansion part）: Overall Response Rate [ Time Frame: up to approximately 36 months ]
   Overall response rate (ORR), defined as a partial response (PR) or complete response (CR) occurring at any point post-treatment according to Response Evaluation Criteria in Solid Tumors as assessed by RECIST v1.1

Secondary Outcome Measures :

1. Number of patients with adverse events (AEs) as a measure of safety and tolerability [ Time Frame: up to approximately 36 months ]
   Safety and tolerability will be assessed through AEs, via monitoring changes in physical examination, clinical laboratory parameters, vital signs and ECGs
2. Disease Control Rate (DCR) [ Time Frame: up to approximately 36 months ]
   DCR, proportion of patients with best overall response of CR, PR or SD
3. Progression-free Survival (PFS) [ Time Frame: up to approximately 36 months ]
   PFS, defined as time from date of treatment to disease progression or death due to any cause
4. Duration of Response (DOR) [ Time Frame: up to approximately 36 months ]
   DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause
5. Overall Survival (OS) [ Time Frame: up to approximately 60 months ]
   OS, defined as time from date of treatment to death due to any cause
6. Maximum observed plasma concentration (Cmax) [ Time Frame: Cycle 1 Day1 and Day 28 ]
   to assess the pharmacokinetic profile
7. Time of maximum observed plasma concentration (Tmax) [ Time Frame: Cycle 1 Day1 and Day 28 ]
   to assess the pharmacokinetic profile
8. Area under the plasma concentration time curve (AUC) [ Time Frame: Cycle 1 Day1 and Day 28 ]
   to assess the pharmacokinetic profile

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed Stage IIIB or IV NSCLC
• Resistance to EGFR TKI (1st, 2nd or 3rd generation)
• Histological or cytological evidence of EGFR mutation and T790M negative after progression on last EGFR TKI therapy
• c-Met GCN ≥ 6 or cluster amplification is required if participant is resistant to1st or 2nd generation EGFR-TKI ;c-MET GCN statue is not required, If participant is resistant to3rd generation EGFR-TKI （osimertinib）；
• Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
• Toxicity recovered to NCI CTCAE v.4.03 Grade ≤1 from previous treatments (except alopecia)
• ECOG performance status (PS) 0 or 1
• Life expectancy of ≥ 12 weeks
• Adequate organ function

Exclusion Criteria:

• Prior treatments

  • Chemotherapy, targeted therapy (except EGFR TKI), immunotherapy, radiotherapy, or major surgery within 4 weeks prior to study treatment
  • Nitrosourea and mitomycin chemotherapy within 6 weeks prior to study treatment
  • EGFR TKI treatment within 2 weeks prior to study treatment
  • Had received live vaccine within 4 weeks prior to study treatment
  • Had received any investigational agent from other clinical study within 4 weeks prior to study treatment or are currently participating in other clinical trials
  • Previous treatment with any other c-MET inhibitor or Axl inhibitor (eg, crizotinib, cabozantinib, volitinib, INC280)
• Symptomatic, untreated or unstable central nervous system metastases
• Spinal cord compression, carcinomatous meningitis or leptomeningeal diseaseonly (patient are only permitted if treated, asymptomatic and stable for at least 4 weeks prior to start of study treatment)
• Interstitial pneumonia or radiation pneumonitis
• Uncontrolled hypertension that require more than two anti-hypertensive agents to control, or systolic blood pressure (BP) >140mmHg or diastolic BP >90 mmHg before the first administration (BP is the mean blood pressure of two measures that 1 hours interval or above)
• Doppler ultrasound evaluation：Left ventricular ejection fraction < 50%
• Grade ≥ 2 of arrhythmia (assessed by NCI CTCAE 4.03), or symptomatic bradycardia, or male with QTCF > 450 ms or female with QTCF > 470 ms, or patients with a history of torsion or congenital QT prolonged syndrome long QT syndrome
• Certain factors that would preclude adequate absorption of CT053PTSA and gefitinib (eg. unable to swallow, chronic diarrhea, intestinal obstruction)
• Significant hemoptysis within 2 months prior to enrollment, or a daily hemoptysis volume is 2.5 ml or above
• Patients with evidence of bleeding tendency, including the following cases: gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above; or melena or hematemesis within 2 months; or visceral bleeding that may occur considered by investigator
• History of immunodeficiency, or other acquired or congenital immunodeficiency, or history of organ transplantation
• Any disease of the following bellowed within 12 months prior to administration: Myocardial infarction, severe angina, or unstable angina, coronary or peripheral artery bypass graft, congestive heart failure, or cerebrovascular events (including transient ischemic attack)
• Pulmonary embolism within 6 months prior to administration
• Active infection of hepatitis B, or infection of HIV
• Other malignancies within 5 years prior to enrollment, with the exception of carcinoma in situ of the cervix, basal or squamous cell skin cancer
• History of thyroid dysfunction, and the thyroid function cannot be maintained at the normal range with drugs.
• Serious electrolyte imbalance in the investigator's judgment
• Pregnant or lactating woman
• Any other reason the investigator considers the patient is not suitable to participate in the study

Contacts and Locations

Contacts

Contact: Li Zhang, MD; (086)020-87343458; zhangli@sysucc.org.cn

Locations

China, Guangdong

Sun Yat-sen University Cancer Center; Recruiting

Guangzhou, Guangdong, China, 510060

Contact: Li Zhang, MD

Principal Investigator: Li Zhang, MD

Sponsors and Collaborators

Sunshine Lake Pharma Co., Ltd.

Investigators

• Principal Investigator: Li Zhang, MD; Sun Yat-sen University

More Information

• Responsible Party: Sunshine Lake Pharma Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03758287
• Other Study ID Numbers: PCD-DCT053-16-001
• First Posted: November 29, 2018
• Last Update Posted: September 18, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gefitinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action