POTENT - Tepotinib in Combination With Pembrolizumab in NSCLC

Sponsor
Institute of Cancer Research, United Kingdom
Study ID
NCT05782361
Phase
PHASE1
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Tepotinib — DRUG
    Tepotinib hydrochloride hydrate will be supplied as film coated tablets. The 250 mg oval, white-pink film-coated tablets contain the excipients mannitol, microcrystalline cellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and Opadry II pink. All formulations are intended for oral administration. Refer to pharmacy manual for formulation and strength information.
  • Pembrolizumab — DRUG
    Pembrolizumab Solution for Infusion 100 mg/vial is a liquid drug product supplied as a clear to opalescent solution, essentially free of visible particles, in Type I glass vials and manufactured using the fully formulated drug substance with L-histidine as buffering agent, polysorbate 80 as surfactant, and sucrose as stabilizer/tonicity modifier. Pembrolizumab Solution for Infusion can be further diluted with normal saline or 5% dextrose in the concentration range of 1 to 10 mg/mL in IV containers made of polyvinyl chloride (PVC) or non-PVC material.

Study Details

This clinical study is looking at the combination of two experimental drugs called tepotinib and pembrolizumab. Pembrolizumab, also known as Keytruda, is licenced and available by prescription to treat a variety of cancers. Tepotinib is currently licensed in the UK for use in non-small cell lung cancer (NCSLC) and is being investigated for this purpose. Cancer immunotherapy drugs hold great promise but still do not work for many patients. Laboratory studies on cancers that do not respond well to immunotherapy reveal that most of these tumours do not have any immune cells. This suggests that the cancer has successfully hidden itself and avoided being recognised by the immune system. This study aims to use a novel approach using a targeted drug, tepotinib, to target the gene involved with NSCLC. Tepotinib is a type of drug called a kinase inhibitor. Kinase inhibitors are a newer type of drug being used to try to treat cancers. They act by blocking some of the chemical messengers that are part of the signalling process within cancer cells that control their growth. Tepotinib is used in adults to treat NSCLC that can have certain abnormal changes in the mesenchymal-epithelial transition factor gene (MET) and which has spread and/or cannot be removed by surgery. The changes in the MET gene can make an abnormal protein which can lead to uncontrolled cell growth and cancer. By blocking this abnormal protein, tepotinib may slow or stop the cancer from growing as well as potentially shrinking the cancer. This study will include patients with and without the MET exon 14 mutations. In this clinical study, the investigators aim to test our ideas in a small number of people for the first time, specifically in those patients with cancers which do not respond to cancer immunotherapy.

Key Dates

Start date
May 3, 2023
Status verified
Aug 2025
Primary completion
Mar 8, 2028
Completion
Jan 9, 2029

Study Design

Enrollment
19 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH

Arms

  • Experimental: Part A- Escalation
    The safety run-in part of the study will enrol 6-12 patients. Tepotinib will be given to patients daily for three weeks. After thee weeks, patients will be given pembrolizumab immunotherapy on a 21-day cycle along side tepotinib daily. Dose de-escalation of Tepotinib only will be performed in in Part A.. Should dose level 1 (500mg OD) be deemed non-tolerable by the SRC then a single dose de-escalation to dose level -1 (250mg OD) may be performed. Alternative dosing schedules may be explored. Recruitment into Part A will be staggered such that at least 7 days elapse between treatment of the 1st and 2nd patient of each dose level. In the dose confirmation phase, the study will first evaluate the dose level 1 with 3 patients, expanding to a maximum of 6 evaluable patients. If needed, a maximum of 6 patients will be evaluate in the dose level -1. Recruitment to this arm is closed.
  • Experimental: Part B- Expansion
    The expansion part of the study will enrol 13-26 patients with NSCLC and MET exon 14 skipping mutations. The combination of tepotinib and pembrolizumab will be tested throughout this part of the study. The first cycle will test the safety run-in of tepotinib followed by the introduction of combination with pembrolizumab from cycle 2 onwards. Recruitment to this arm is open.

Primary Outcome Measure

Anti-tumour activity evaluation (in Part B) [ Time Frame: 24 Months ]

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