Trial Title:
POTENT - Tepotinib in Combination with Pembrolizumab in NSCLC
NCT ID:
NCT05782361
Condition:
Advanced Cancer
Non Small Cell Lung Cancer
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Pembrolizumab
Tepotinib
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Health Services Research
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tepotinib
Description:
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.
Arm group label:
Part A- Escalation
Arm group label:
Part B- Expansion
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
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.
Arm group label:
Part A- Escalation
Arm group label:
Part B- Expansion
Other name:
MK-3475
Summary:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female patients aged 18 or over.
2. Non-small cell lung cancer histologically confirmed
3. Part A:
Either
1. Exon 14 MET mutation (on tissue or ctDNA testing)
2. Patients have not received systemic therapy for advanced non-small cell lung
cancer Or
1. Patient has received at least one line of systemic anticancer therapy for
metastatic disease
2. Patient has received at least two cycles of immune checkpoint inhibitor and has
demonstrated disease progression within 12 weeks of last dose
4. Part B:
Cohort 1 c) Exon 14 MET mutation (on tissue or ctDNA testing) d) Patients have not
received systemic therapy for advanced non-small cell lung cancer
5. Measurable disease as assessed by iRECIST
6. Life expectancy of at least 12 weeks.
7. World Health Organisation (WHO) performance status of 0 or 1.
8. Haematological and biochemical indices within the ranges shown below. These
measurements must be performed within one week (Day -7 to Day 1) prior to the
patient's first dose of IMP.
9. Written (signed and dated) study informed consent and be capable of co-operating
with treatment and follow-up. If patient does not comply with study procedures such
that safety of the trial is affected then they will be withdrawn from the study.
10. Female patients with reproductive potential must have a negative urine or serum
pregnancy test performed within 7-days prior to start of trial.
Laboratory test requirements:
Haemoglobin (Hb)
- 9.0 g/dL Absolute neutrophil count
- 1.5 x 109/L Platelet count
- 100 x 109/L Serum bilirubin
- 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST)
- 2.5 x (ULN) unless raised due to tumour in which case up to 5 x ULN is
permissible Renal function
Either:
Serum creatinine
≤ 1.5 x upper limit of normal (ULN) Or Calculated creatinine clearance (using the Wright,
Cockcroft & Gault formula) GFR ≥ 50 mL/min (uncorrected value) Coagulation INR < 1.5 APTT
<1.5x ULN Unless participant is receiving anticoagulant therapy as long as PT or aPTT is
within therapeutic range of intended use of anticoagulants
Exclusion Criteria:
1. Radiotherapy, endocrine therapy, immunotherapy or chemotherapy during the previous
four weeks (six weeks for nitrosoureas, Mitomycin-C) and four weeks for
investigational medicinal products), except for bisphosphonates or RANK ligand
antagonists that are permitted for the management of bone metastases. Radiotherapy
at radical doses within 6 months.
2. Ongoing Grade 2 or greater toxicities of previous treatments. Exceptions to this are
alopecia and ongoing anticoagulation therapy due to prior thromboembolic episodes.
3. History of ILD or interstitial pneumonitis requiring steroid administration.
4. Ability to become pregnant (or already pregnant or lactating). However, those female
patients who have a negative serum or urine pregnancy test before enrolment and
agree to use two highly effective forms of contraception (oral, injected or
implanted hormonal contraception and condom, have an intra-uterine device and
condom) for four weeks before entering the trial, during the trial and for six
months afterwards are considered eligible.
5. Male patients with partners of child-bearing potential (unless they agree to take
measures not to father children by using a barrier method of contraception [condom
plus spermicide] or to sexual abstinence effective from the first administration of
IMP throughout the trial and for six months afterwards. Men with partners of
child-bearing potential must also be willing to ensure that their partner uses an
effective method of contraception for the same duration for example, hormonal
contraception, intrauterine device, diaphragm with spermicidal gel or sexual
abstinence). Men with pregnant or lactating partners must be advised to use barrier
method contraception (for example, condom plus spermicidal gel) to prevent exposure
of the foetus or neonate.
NB. Abstinence is only considered to be an acceptable method of contraception when
this is in line with the preferred and usual lifestyle of the subject. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and
withdrawal are not acceptable methods of contraception.
6. Known untreated or active central nervous system (CNS) metastases (progressing or
requiring corticosteroids for symptomatic control). Patients with a history of
treated CNS metastases are eligible, provided they meet all of the following
criteria:
- Evaluable or measurable disease outside the CNS is present.
- Radiographic stability upon the completion of CNS-directed therapy and no
evidence of interim progression between the completion of CNS-directed therapy
and the baseline disease assessment
- Not requiring corticosteroids.
7. Major surgery within four weeks of the first dose of study treatment.
8. At high medical risk because of non-malignant systemic disease including active
uncontrolled infection.
9. Known to be serologically positive for hepatitis B, hepatitis C or human
immunodeficiency virus (HIV).
10. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 14 days prior to the first dose of
trial treatment.
11. Has an active autoimmune disease that has required systemic treatment in past 3
months (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment. Patients with a
history of inflammatory bowel diseases such as Crohn's disease or ulcerative colitis
will be excluded from the study. Patients with Sjogren's syndrome will not be
excluded from the study. In addition, patients that experienced a Grade 2 or higher
immune-related AEs on treatment with immunotherapy will be excluded from the study.
Patients with inactive autoimmune disease which has previously required systemic
therapy, may be considered on a case-by-case basis after discussion with the chief
investigator.
12. Has a known history of severe allergic anaphylactic reactions to chimeric, human or
humanized antibodies, or fusion proteins.
13. Has received a live vaccine within 30 days of planned start of study therapy. Note:
The killed virus vaccines used for seasonal influenza vaccines for injection are
allowed; however intranasal influenza vaccines (e.g. FluMist®) are live attenuated
vaccines and are not allowed.
14. Previous treatment with tepotinib or other selective/unselective MET inhibitor
15. Experience hypersensitivity to tepotinib, pembrolizumab or any of their excipients.
16. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 consecutive
electrocardiograms (ECGs) within 5 minutes of each other. Known congenital QT
syndrome or history of torsades de pointes.
- Any clinically significant abnormalities in rhythm, conduction or morphology of
resting ECG, e.g. complete left bundle branch block, third degree heart block.
Controlled atrial fibrillation is allowed.
- Experience of any of the following procedures or conditions in the preceding 6
months: coronary artery bypass graft, angioplasty, vascular stent, myocardial
infarction, angina pectoris, congestive heart failure New York Heart
Association [NYHA Grade 2 or above], severe valvular disease, uncontrolled
hypertension despite optimal therapy.
17. Prior bone marrow transplant or have had extensive radiotherapy to greater than 25%
of bone marrow within eight weeks.
18. Current malignancies of other types, with the exception of adequately treated cone
biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma
of the skin. An exception to this criteria are cancer survivors, who have undergone
potentially curative therapy for a prior malignancy, have no evidence of that
disease for three years or more and are deemed at negligible risk for recurrence,
are eligible for the trial.
19. Is a participant or plans to participate in another interventional clinical trial,
whilst taking part in this Phase I study. Participation in an observational trial
would be acceptable.
20. Any other condition which in the Investigator's opinion would not make the patient a
good candidate for the clinical trial.
21. Symptoms of active COVID-19 and/or documented active COVID-19 infection at the time
of screening.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
DDU, Royal Marsden Hospital NHS Foundation Trust
Address:
City:
Sutton
Zip:
SM2 5PT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Anna Minchom, MD
Phone:
+442086426011
Email:
POTENT@icr.ac.uk
Contact backup:
Last name:
Anna Minchom, MD
Facility:
Name:
University College London Hospitals NHS Foundation Trust
Address:
City:
London
Zip:
NW1 2BU
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Martin Forster, MD
Phone:
+442034567890
Email:
POTENT@icr.ac.uk
Facility:
Name:
Lung Unit, Royal Marsden Hospital NHS Foundation Trust
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Prof Sanjay Popat, MD
Phone:
+442073528171
Email:
POTENT@icr.ac.uk
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Colin Lindsay, MD
Phone:
+441614463000
Email:
POTENT@icr.ac.uk
Contact backup:
Last name:
Colin Lindsay, MD
Start date:
May 3, 2023
Completion date:
February 1, 2028
Lead sponsor:
Agency:
Institute of Cancer Research, United Kingdom
Agency class:
Other
Collaborator:
Agency:
Merck Healthcare KGaA
Agency class:
Other
Source:
Institute of Cancer Research, United Kingdom
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05782361
