Phase II study of MRTX849 monotherapy and in combination with pembrolizumab in patients with advanced non-small-cell lung cancer with KRAS G12C mutation
| ISRCTN | ISRCTN13464104 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13464104 |
| ClinicalTrials.gov (NCT) | NCT04613596 |
| Clinical Trials Information System (CTIS) | 2020-003101-58 |
| Integrated Research Application System (IRAS) | 1004279 |
| Protocol serial number | 849-007, IRAS 1004279, CPMS 51494 |
| Sponsor | Mirati Therapeutics (United States) |
| Funder | Mirati Therapeutics |
- Submission date
- 24/02/2022
- Registration date
- 03/05/2022
- Last edited
- 09/11/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
The aim of this study is to evaluate the effectiveness of the investigational medication MRTX849, given alone or in combination with the cancer therapy pembrolizumab, in patients with non-small cell lung cancer (NSCLC) who have a specific change in a tumour gene (KRAS G12C mutation). This evaluation will include looking at how effective this treatment is in reducing and controlling the cancer. Other aims of the study include assessing what side effects occur and how often they occur, how quickly MRTX849 is absorbed into the bloodstream, and how fast it is removed by the body. Several laboratory tests will be performed using samples of tumour tissue or blood to understand how and why the combination of medications may work.
Who can participate?
Patients with advanced non-small-cell lung cancer with KRAS G12C mutation
What does the study involve?
Participants will be randomly allocated to one of three treatment groups that will receive either MRTX849 and pembrolizumab or MRTX849 alone. Study treatment will be administered in 21-day cycles until one of the indications for stopping treatment is identified such as disease progression, unacceptable adverse reaction(s) or receipt of the maximum number of cycles per local standard-of-care.
What are the possible benefits and risks of participating?
The potential risks and burdens for this study are provided in the participant information sheet and informed consent forms. The participants will therefore know about these risks and burdens before taking part in the study. Study staff will be trained on the expected side effects associated with the study drugs. They will also be trained on how to report unexpected reactions and given the contact details for the appropriate contact to discuss management and treatment of these side effects. Female participants are advised not to become pregnant during the study or within 6 months of completing treatment. Pregnancy tests will be performed before the administration of the study drugs. Both male and female participants are advised to use contraception for the duration of participation in the study. Should a partner of a participant become pregnant during this study they will be advised on the risks and will be invited to consent to additional assessment of the mother and child by the study team during and after the pregnancy.
Where is the study run from?
Mirati Therapeutics (USA)
When is the study starting and how long is it expected to run for?
February 2022 to August 2024
Who is funding the study?
Mirati Therapeutics (USA)
Who is the main contact?
Vicky Kang
miratistudylocator@emergingmed.com
Contact information
Scientific
Senior Medical Director, Clinical Development
Mirati Therapeutics, Inc.
3545 Cray Court
San Diego
CA 92121
United Kingdom
| Phone | +1 844 893 5530 |
|---|---|
| miratistudylocator@emergingmed.com |
Principal investigator
Wilmslow Road
Manchester
M20 4BX
United Kingdom
| Phone | +44 (0)161 9182514 |
|---|---|
| colin.lindsay@manchester.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomized controlled trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | A Phase II trial of MRTX849 monotherapy and in combination with pembrolizumab in patients with advanced non-small-cell lung cancer with KRAS G12C mutation |
| Study objectives | 1. To evaluate the efficacy of MRTX849 monotherapy and in combination with pembrolizumab administered in the first-line treatment setting to patients having non-small-cell lung cancer (NSCLC) with KRAS G12C mutation 2. To characterize the safety and tolerability of the monotherapy and the combination regimen in the selected population 3. To evaluate secondary efficacy endpoints using monotherapy and the combination regimen in the selected population 4. To evaluate the pharmacokinetics (PK) of MRTX849 administered as monotherapy and in combination with pembrolizumab |
| Ethics approval(s) | Approval pending, REC ref: 22/EE/0062 |
| Health condition(s) or problem(s) studied | Advanced non-small cell lung cancer |
| Intervention | This is a study involving an investigational (experimental) medication called MRTX849, being developed by Mirati Therapeutics, Inc. In this study, participants will be administered MRTX849 monotherapy (alone) or MRTX849 in combination with pembrolizumab, an immunotherapy that has not yet been approved by the regulatory authorities such as the Medicines & Healthcare products Regulatory Agency (MHRA) in the UK for the treatment of lung cancer in several settings. The study will include participants with locally advanced or metastatic NSCLC harbouring the KRAS-G12C mutation. Participants will be enrolled and treated in three cohorts (groups) as defined by their tumour proportion score (TPS) determined through assessment of extra signal molecules (PD-L1 molecules) found on the surface of the tumour cells. Up to 250 participants across approximately 110 study sites globally are expected to participate in this study. Participants in this study will receive treatment based on the results of their PD-L1 testing (a marker that looks at how the immune system is involved in a cancer). If the PD-L1 result is “negative” (less than (<) 1%), the participants will be randomly assigned to one of two groups through an online tool called IRT, to receive the following treatments listed below: Cohort 1a: MRTX849 (400 mg dose) twice daily in combination with a standard treatment for lung cancer (pembrolizumab) OR Cohort 1b: MRTX849 (600 mg dose) twice daily If the PD-L1 result is “positive” (1% or (>) greater), the participant will receive the following treatment listed below: Cohort 2: MRTX849 (400 mg dose) twice daily in combination with (pembrolizumab) which is the standard treatment for lung cancer. Participants may remain on the study treatment for as long as their disease doesn’t get worse such that the study doctor feels they should stop study treatment, and as long as they tolerate the medication (the side effects are not typically severe), and they wish to continue. All participants will be followed for adverse events (AEs) for at least 28 days after the last dose of study treatment. All participants will be followed for serious adverse events (SAEs) for 90 days following the last dose of study treatment or, if subsequent therapy is begun, at least 28 days following the last dose of study treatment. For participants who discontinue study treatment for a reason other than objective disease progression, disease assessment should continue until objective disease progression is documented by the investigator or start of subsequent anti-cancer therapy, whichever is sooner. Survival status and subsequent anti-cancer therapies will be collected during long term follow-up until death or lost to follow-up. |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | MRTX849, pembrolizumab |
| Primary outcome measure(s) |
Objective Response Rate (ORR) assessed using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 at 22 months |
| Key secondary outcome measure(s) |
1. Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities at 22 months |
| Completion date | 31/08/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 250 |
| Key inclusion criteria | 1. Histologically confirmed diagnosis of NSCLC (squamous or nonsquamous) with KRAS G12C mutation and known PD-L1 Tumor Proportion Score (TPS) score 2. Unresectable or metastatic disease |
| Key exclusion criteria | 1. Prior systemic treatment for locally advanced or metastatic NSCLC including chemotherapy, immune checkpoint inhibitor therapy, or a therapy targeting KRAS G12C mutation (e.g., AMG 510) 2. Active brain metastases |
| Date of first enrolment | 23/11/2020 |
| Date of final enrolment | 31/08/2023 |
Locations
Countries of recruitment
- United Kingdom
- England
- Scotland
- Australia
- Austria
- Belgium
- Canada
- China
- Germany
- Hungary
- Ireland
- Israel
- Italy
- Netherlands
- New Zealand
- Poland
- Portugal
- Singapore
- Spain
- Taiwan
Study participating centres
Withington
Manchester
M20 4BX
United Kingdom
Leicester
LE1 5WW
United Kingdom
Edgbaston
Birmingham
B15 2GW
United Kingdom
Edinburgh
Lothian
EH4 2XU
United Kingdom
London
SE1 9RT
United Kingdom
Guildford
GU2 7XX
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Published as a supplement to the results publication |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
09/11/2022: The scientific contact was changed and the plain English summary was updated accordingly.
07/06/2022: Internal review.
30/04/2022: ISRCTN received notification of combined HRA/MHRA approval for this trial on 30/04/2022.
24/02/2022: Trial's existence confirmed by the HRA.
