Phase 1b/2a, Open-label Study of Vactosertib in Combination With Durvalumab in Advanced NSCLC

NCT03732274 | Completed Phase 1 DMC

• 1 other identifier: MP-VAC-203
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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.

Conditions

Non-Small Cell Lung Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  To define the MTD

  4 weeks

Secondary Outcomes (4)

• 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)

Study Arms (1)

Dose Escalation of TEW-7197

EXPERIMENTAL

TEW-7197 will be administered orally for 5 days per week (5D/W) and Durvalumab administration.

Drug: TEW-7197

Interventions

TEW-7197 DRUG

TEW-7197 will be administered orally for 5 days per week (5D/W) at the same time in the morning and evening (BID) approximately 12 hours apart. Durvalumab will be administered as a dose of 1500 mg every 4weeks.

Also known as: vactosetib

Dose Escalation of TEW-7197

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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-L1.
• All patients must be able to provide an available tumor sample collected within ≤3 years after the last anticancer therapies prior to screening. At least 25 patients enrolled in the dose expansion phase must be able to provide newly acquired tumor biopsy taken within 6 months prior to the first dosing. Tumor lesions used for newly acquired biopsies should not be target lesions, unless there are no other lesions suitable for biopsy, and only a core needle (not excisional/incisional) biopsy is allowed when biopsies are performed on target lesions as there is no other lesions suitable for biopsy. In patients with only one target lesion, biopsy for baseline tumor evaluation should be performed prior to the imaging test with an interval of at least 2 weeks after biopsy. Samples with limited tumor content and fine needle aspirate specimens are not acceptable. Specimens from metastatic bone lesions are typically unacceptable unless there is a significant soft tissue component. The tumor specimen quantity should be as sufficient as possible to allow for exploratory biomarker analyses and is preferred in formalin-fixed paraffin embedded blocks. An additional subsequent tumour biopsy will be performed on C2D3-6 or C2D10-13 only in patients who provide newly acquired tumor biopsy taken within 6 months prior to the first dosing. The same tumor lesion should be biopsied at all timepoints, if feasible, to avoid introduction of heterogeneity related to the site of tumor or metastasis.
• Adequate organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count ≥1.0 × 109 /L
• Platelet count ≥75 × 109/L

You may not qualify if:

• 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
• Adequately treated carcinoma in situ without evidence of disease
• History of leptomeningeal carcinomatosis
• History of active primary immunodeficiency
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (HBV surface antigen \[HBsAg\] test positive), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody (anti-HBc) and negative of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only with negative HCV RNA measured by polymerase chain reaction.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.

Sponsors & Collaborators

• MedPacto, Inc.: lead
• AstraZeneca: collaborator

Study Sites (4)

ChungBuk national university hospital

Chungju, South Korea

Location

National Cancer Center

Goyang-si, South Korea

Location

Yeonsei University Hospital

Seoul, South Korea

Location

The Catholic univ of korea st.vincent's hospital

Suwon, South Korea

Location

Study Officials

• Minkyu Heo

  MedPacto, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2018
• First Posted: November 6, 2018
• Study Start: February 11, 2019
• Primary Completion: May 17, 2024
• Study Completion: May 17, 2024
• Last Updated: April 10, 2025

Record last verified: 2025-04

Locations

KR (4)