Phase 1b/2a, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib in Combination With Durvalumab in Patients With Advanced Non Small Cell Lung Cancer Who Progressed Following Platinum-based Chemotherapy
Overview
- Phase
- Phase 1
- Intervention
- TEW-7197
- Conditions
- Non-Small Cell Lung Cancer Metastatic
- Sponsor
- MedPacto, Inc.
- Enrollment
- 60
- Locations
- 4
- Primary Endpoint
- Maximum Tolerated Dose
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is an open -label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib in Combination with durvalumab in patients advanced NSCLC who progressed following platinum-based chemotherapy.
Detailed Description
This is Phase 1b/2a, open label, multi-center study to assess safety, tolerability, pharmacokinetics and anti-tumor activity of vactosertib in combination with durvalumab in patients advanced NSCLC. This study has been designed to allow for an investigation of the optimal dose of vactosertib in combination with durvalumab. There are two parts to this study: Phase 1b, vactosertib dose-escalation study to determine the recommended phase 2 dose (RP2D) and Phase 2a, non-randomized parallel dose expansion study to confirm RP2D. In the current dose-escalation (Phase 1b) study to determine RP2D, vactosertib dosing will begin at 100 mg BID for 5 days per week in combination with durvalumab 1500 mg, Q4W. According to the following dose escalation rule, 200 mg BID oral dose as maximum administered dose (MAD) will be administered in combination with durvalumab. This phase 2a study is a study designed to evaluate the anti-tumor effects of vactosertib in combination with durvalumab in a total of 45 patients with PD-L1 positive advanced NSCLC who progressed following platinum-based chemotherapy (no prior immunotherapy)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- •Age ≥19 years at the time of screening
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrollment
- •Histological or cytological confirmation of advanced NSCLC who progressed following platinum-based chemotherapy.
- •If there is measurable disease based on RECIST 1.1 identified by the investigator at screening and there is at least one non-irradiated lesion suitable for selection as a target lesion according to RECIST 1.1 on imaging test, tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to the first dose.
- •No prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines for treatment purpose.
- •In dose escalation phase, 6 DLT evaluable patients whose tumor cell PD-L1 expression less than 25% will be enrolled in each cohort. In dose expansion phase, 45 patients with confirmed PD-L1-positive NSCLC by using the Ventana SP263 IHC assay will be enrolled
- •Evaluation in newly acquired tumor tissue (preferred) or archival tissue (≤3 years old).
- •If the patient's PD-L1 status has already been assessed using Ventana SP263 assay, this test result can be used to assess eligibility for enrollment.
- •Note: A positive PD-L1 sample is measured using a defined cut-off based on ≥1% of tumor cells with membrane staining of any intensity for PD-L
Exclusion Criteria
- •History of allogeneic organ transplantation.
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
- •Patients with vitiligo or alopecia
- •Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
- •Any chronic skin condition that does not require systemic therapy
- •Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
- •Patients with celiac disease controlled by diet alone
- •Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association \[NYHA\] Class III/IV), uncontrolled hypertension (≥150/90 mmHg), unstable angina pectoris, myocardial infarction (≤ 6 months prior to screening), clinically significant cardiac valvulopathy requiring treatment, uncontrolled cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
- •History of another primary malignancy except for
- •Malignancy tumors with low risk of recurrence treated with curative intent and with no known active disease ≥5 years before the first dose of IP Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Arms & Interventions
Dose Escalation of TEW-7197
TEW-7197 will be administered orally for 5 days per week (5D/W) and Durvalumab administration.
Intervention: TEW-7197
Outcomes
Primary Outcomes
Maximum Tolerated Dose
Time Frame: 4 weeks
To define the MTD
Secondary Outcomes
- Number of participants with treatment -related adverse events(From screening through study completion (up to 28 days after the last dose of Investigational Drug))
- Objective Response Rate (%)(every 2 cycles (each cycle is 28 days) and end of treatment (EOT) time point ,EOT is defined as within 30 days from the last dose of study medication by the protocol)
- Pharmacokinetics (PK) of TEW-7197(At cycle 1 (each cycle is 28 days))
- Pharmadynamics of TEW-7197(At cycle 1 ,3 (each cycle is 28days))