TATE and Pembrolizumab (MK3475) in mCRC and NSCLC

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

Detailed Description
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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.

Official Title
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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

Conditions
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Colorectal Cancer; Lung Cancer

Intervention / Treatment
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* Drug: TATE and pembrolizumab
* Drug: TAS-102 pill
* Drug: Regorafenib Pill


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label study in two indications. The mCRC cohort will be a randomized trial for TATE+Pembrolizumab versus standard 3rd line therapy for mCRC. The NSCLC cohort will be single-arm study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: colorectal cancer<br>metastatic colorectal cancer progressed on at least two lines of chemotherapy | Drug: TATE and pembrolizumab<br>* 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.<br>* Other names: TATE: Trans-arterial Tirapazamine Embolization;;Drug: TAS-102 pill<br>* The comparator of the mCRC arm is TAS-102 at 60 mg BID 5 days per week for 2 weeks then 2 weeks off.<br>* Other names: LONSURF;Drug: Regorafenib Pill<br>* 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.<br>* Other names: STIVARGA;|
| Experimental: NSCLC<br>Liver metastatic NSCLC progressed on immune checkpoint inhibitors and chemotherapy | Drug: TATE and pembrolizumab<br>* 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.<br>* Other names: TATE: Trans-arterial Tirapazamine Embolization;;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal cancer, NSCLC, pembrolizumab, tirapazamine, Liver metastasis