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TERMINATEDPHASE2

Study of TH-302 or Placebo in Combination With Pemetrexed in Patients With Non-squamous Non-small Cell Lung Cancer

A Randomized Phase 2, Double-blind, Placebo-controlled, Multi-center Study Comparing Pemetrexed in Combination With TH-302 vs. Pemetrexed in Combination With Placebo as Second-line Chemotherapy for Advanced Non-Squamous, Non-Small Cell Lung Cancer

NCT02093962•ImmunoGenesis

View on ClinicalTrials.gov

Summary

The purpose of this study is to determine whether TH-302 in combination with pemetrexed is safe and effective in the treatment of non-squamous non-small cell lung cancer.

Detailed Description

TH-302 is designed to target the hypoxic regions of tumors which are generally located distant from tumor vessels. Pemetrexed has poor tissue penetration and targets the regions of tumors that are located in proximity to the tumor vessels. The presence of hypoxia in solid tumors is associated with a more malignant phenotype and resistance to chemotherapy. The hypoxia-activated prodrug, TH-302, is designed to selectively target the hypoxic microenvironment. There is evidence supporting the presence of hypoxia in NSCLC lesions based on a hypoxia PET study. Combining pemetrexed with TH-302 may enable the targeting of both the normoxic and hypoxic regions of NSCLC lesions.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Men and women ≥ 18 years of age.
•Histologically or cytologically confirmed stage IIIB or IV NSCLC with non-squamous histology
•Recurrent or progressive disease after one prior platinum-based non-pemetrexed chemotherapy treatment for advanced disease with or without maintenance
•Neoadjuvant/adjuvant cytotoxic chemotherapy initiated \< 12 months prior to study randomization will be counted as one prior treatment
•Neoadjuvant/adjuvant cytotoxic chemotherapy initiated ≥ 12 months prior to study randomization will not be counted as one prior chemotherapy treatment
•Use of targeted agents (e.g., monoclonal antibodies or kinase inhibitors) will not be counted as a prior chemotherapy treatment
•Patients with known EGFR-activating mutations or ALK rearrangements should have received treatment with a targeted kinase inhibitor (e.g., erlotinib, crizotinib) and no longer be considered as a candidate for such treatment
•Measurable disease according to RECIST 1.1
•ECOG performance status 0-1
•Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects of prior therapy
+2 more criteria

Exclusion Criteria

•Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung or NSCLC NOS
•Prior therapy with pemetrexed
•Inability or unwillingness to take folic acid, vitamin B12 supplementation or corticosteroids
•Inability to discontinue non-steroidal anti-inflammatory drugs for 5 days (long half-life) or for 2 days (short half-life, if CrCL \<80 mL/min) before pemetrexed dosing and until 2 days after pemetrexed dosing
•Leptomeningeal disease or any untreated or symptomatic brain metastases, unless the following criteria are met:
•* brain metastases are stable and have been previously treated with either whole-brain radiotherapy or gamma-knife surgery
•* steroids are currently not required and more than 14 days since last steroid treatment
•Symptomatic pleural effusion (\> CTCAE Grade 1 dyspnea) that is not amenable to drainage
•Treatment with other systemic anticancer therapy within 4 weeks prior to the first dose of study medication
•Treatment with full field radiation therapy within 4 weeks or limited field radiation therapy within 2 weeks prior to the first dose of study medication
+9 more criteria

Locations (80)

UAB Cancer Center

Birmingham, Alabama, United States

Ironwood Cancer and Research Centers

Chandler, Arizona, United States

California Cancer Center

Encinitas, California, United States

California Cancer Center Associates

Fresno, California, United States

UCLA-Department of Medicine a Division of Hem/Onc

Los Angeles, California, United States

Sarcoma Oncology Research Center

Santa Monica, California, United States

VA Eastern Colorado Healthcare System

Denver, Colorado, United States

Christiana Care Health Services

Newark, Delaware, United States

Cancer Specialists of North Florida - CBO

Jacksonville Beach, Florida, United States

AMPM Research

Miami, Florida, United States

Key Dates

Start Date

June 1, 2014

Primary Completion Date

April 1, 2016

Completion Date

May 1, 2016

Last Updated

May 16, 2025

Enrollment

265

ACTUAL participants

Conditions

Non-small Cell Lung Cancer

Interventions

TH-302 combination with pemetrexed

DRUG

Matched placebo in combination with pemetrexed

DRUG

Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

NCT06305754

Non-small Cell Lung Cancer (NSCLC)

View study

RECRUITINGPHASE3

A Clinical Study of Calderasib (MK-1084) and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007)

NCT07190248

Non-small Cell Lung Cancer

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 16, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Study of TH-302 or Placebo in Combination With Pemetrexed in Patients With Non-squamous Non-small Cell Lung Cancer

Inclusion Criteria

Exclusion Criteria

Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

A Clinical Study of Calderasib (MK-1084) and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007)

Study of Izalontamab Brengitecan (BMS-986507) Versus Platinum-Pemetrexed for EGFR-mutated Non-small Cell Lung Cancer After Failure of EGFR TKI Therapy (IZABRIGHT-Lung01)

Beamion LUNG-3: A Study to Test Whether Zongertinib Helps People With Surgically Removed, Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment

Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations

Reduced CT + Anti-PD-1 as First Line Tx in Vulnerable Older Adults w/Adv <50% PD-L1 Non-Small Cell Lung Cancer (NSCLC)