TATE and Pembrolizumab (MK3475) in mCRC and NSCLC

An Open Label Phase II Study for the Treatment of Liver Metastatic Colorectal Cancer and Non-Small Cell Lung Cancer With a Combination of TATE (Trans-Arterial Tirapazamine Embolization) and Pembrolizumab

Patients with refractory metastatic colorectal cancer or non-small cell lung cancer with liver metastasis treated with Trans-arterial Tirapazamine Embolization along with Pembrolizumab.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Lung Cancer
• Intervention / Treatment: Drug: TATE and pembrolizumab; Drug: TAS-102 pill; Drug: Regorafenib Pill

Detailed Description

This study is an open-label study to treat patients with refractory metastatic colorectal cancer and non-small cell lung cancer with liver metastasis. Patients enrolled in the mCRC cohort will be randomized to receive study treatment Trans-arterial Tirapazamine Embolization (TATE)+Pembrolizumab or FDA-approved standard of care, such as TAS-102 or regorafenib, and their Overall Survival (OS) will be compared in the two cohorts as the primary endpoint. Patients enrolled in the NSCLC cohort will all receive study treatment TATE+Pembrolizaumb and Overall Response Rate (ORR) will be the primary endpoint.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ray Lee, MD. PhD.; Phone Number: 8043341076; Email: ray.lee01@teclison.com
• Study Contact Backup: Name: Chiwei Lu; Email: chiwei.lu4@teclison.com

Study Locations

• Taiwan
  • Hsinchu, Taiwan
    • Recruiting
    • China Medical University Hsinchu Hospital
    • Contact: Sandy Lai; Email: sandy6618@teclison.com
  • Taichung, Taiwan
    • Recruiting
    • Chung Shan Medical University Hospital
    • Contact: Sandy Lai; Email: sandy6618@teclison.com
• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine Medical Center
      • Contact: Miranda Duron; Email: mnduron@hs.uci.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Liver metastatic MSS-mCRC or NSCLC without EGFR or AKT mutations
• mCRC progressed on at least two lines of standard chemotherapy; or
• NSCLC progressed on chemotherapy and an immune checkpoint inhibitor
• Measurable disease
• ECOG 0-1
• At least 4 weeks from prior chemotherapy and free from chemo-related toxicity
• Adequate organ function

Exclusion Criteria:

• Prior organ transplantation
• Liver metastasis more than 50%
• Oxygen saturation less than 92% in room air
• Prior autoimmune disorder
• CNS metastasis
• Major GI bleeding in the last 2 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: colorectal cancer; metastatic colorectal cancer progressed on at least two lines of chemotherapy	Drug: TATE and pembrolizumab; All liver metastatic lesions will be treated with TATE for maximally debulking. Pembrolizumab IV infusion per standard schedule every 3 or 6 weeks until progression or maximally 2 years.; Other Names: TATE: Trans-arterial Tirapazamine Embolization; Drug: TAS-102 pill; The comparator of the mCRC arm is TAS-102 at 60 mg BID 5 days per week for 2 weeks then 2 weeks off.; Other Names: LONSURF; Drug: Regorafenib Pill; As an alternative to TAS-102 per treating physician's discretion. If selected, Regorafenib 160 mg oral daily for 3 weeks on and one week off, every 4 weeks per cycle. Do not take Regoarefnib if taking TAS-102.; Other Names: STIVARGA
Experimental: NSCLC; Liver metastatic NSCLC progressed on immune checkpoint inhibitors and chemotherapy	Drug: TATE and pembrolizumab; All liver metastatic lesions will be treated with TATE for maximally debulking. Pembrolizumab IV infusion per standard schedule every 3 or 6 weeks until progression or maximally 2 years.; Other Names: TATE: Trans-arterial Tirapazamine Embolization;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival for the mCRC cohort	From the first day of treatment to death	24 months
Overall Response Rate (ORR) for the NSCLC cohort	Per RECIST 1.1 criteria	within 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response	per RECIST 1.1	24 months
Response rate	in TATE treated or TATE-untreated lesions by RECIST and mRECIST	24 months
PFS	Progression Free Survival	24 months
TTP	Time to Progression	24 months

Collaborators and Investigators

• Sponsor: Teclison Ltd.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Ray Lee, Teclison Limited

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2021
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: colorectal cancer; NSCLC; pembrolizumab; Liver metastasis; tirapazamine
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Neoplasms; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Tirapazamine
• Other Study ID Numbers: LT-007; KEYNOTE-A91 (Other Identifier: Merck & Co.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: International meeting report or medical Journal publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No