TACTI-002 (P015); Keynote-PN798 (Two ACTive Immunotherapeutics)
Research type
Research Study
Full title
TACTI-002 (Two ACTive Immunotherapeutics): A multicenter, open label, Phase II study in patients with previously untreated unresectable or metastatic non-small cell lung cancer (NSCLC), or recurrent PD-X refractory NSCLC or with recurrent or metastatic squamous head and neck cancer (HNSCC) receiving the soluble LAG-3 fusion protein eftilagimod alpha (IMP321) in combination with pembrolizumab (PD-1 antagonist)
IRAS ID
250623
Contact name
Martin Forster
Contact email
Sponsor organisation
Immutep S.A.S.
Eudract number
2018-001994-25
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Research Summary
The primary objective of this study is to evaluate the response rate of eftilagimod alpha in combination with pembrolizumab in patients with advanced, metastatic, recurrent NSCLC and HNSCC.
First patient first visit is envisaged for Q.4/2018. The recruitment time for stage 1 is estimated to be 9 months. The primary completion date for stage 1 is estimated within H1/2019. In case stage 2 is opened the first patient first visit is expected for H1/2019. The recruitment time for stage 2 is estimated to be 9 months. The primary completion date for stage 1+2 is H2 2020.
The proposed phase II clinical study aims to determine the response rate, safety and further antitumor activity of eftilagimad alpha in combination with the anti-PD-1 antagonist pembrolizumab in patients with advanced, metastatic, recurrent non-small cell lung cancer and squamous head and neck cancer. Based on the complementary mechanism of action, the presented preclinical and clinical data it is believed that the addition of efti to pembrolizumab therapy increases the response rates of pembrolizumab in these indications.
Summary of Results
CLINICAL TRIALS LAY SUMMARY OF THE RESULTS
TACTI-002 STUDY (IMP321-P015)
Study that tested new drug eftilagimod alpha (also known as efti) with a marketed drug called pembrolizumab in late-stage non–small cell lung cancer (NSCLC) that has not been treated or cannot be removed by surgery, NSCLC that has come back and doesn’t respond to PD-1 treatments, or advanced head and neck cancer that has come back or spread.
Welcome
Researchers need many studies to decide which medicines work best and are safest. This summary explains how this particular study was done and what the results were.
1. WHAT WERE THE BACKGROUND AND OBJECTIVES OF THE STUDY?
Late-stage non-small cell lung cancer (NSCLC) is a type of lung cancer that has spread to other parts of the body (metastatic) or came back after successful treatment (recurrent). If it cannot be removed by surgery (unresectable), treatment choice depends on whether the cancer has certain gene mutations. If no genetic mutations are found in the cancer cells, treatment will consist of immunotherapy alone or in combination with chemotherapy. Immunotherapy refers to a type of drug that helps the immune system fight the cancer.
In some cases, late-stage NSCLC continues to grow or comes back even after initial treatment with immunotherapy. PD-1 (programmed death 1) and PD-L1 (programmed death-ligand 1) are proteins that help cancer cells hide from attacks by the immune system. Lung cancer that has stopped responding to treatments that target the PD-1 or PD-L1 proteins is called PD-1 or PD-L1 refractory NSCLC.
Head and neck cancer refers to a group of cancer that begin in certain parts of the head and neck, such as the mouth, throat, and voice box. If the cancer spreads to other parts of the body, it is called metastatic head and neck cancer.
Efti, or eftilagimod alpha, boosts the immune response to fight tumours. It activates a specific type of immune cell known as dendritic cells. Once activated, dendritic cells then help to switch on other immune cells that kill cancer cells.
Pembrolizumab is an approved immunotherapy currently used to treat several cancer types. It helps the immune system find and attack cancer cells by blocking the PD-1 protein that cancer uses to stay hidden.
The combination of efti and pembrolizumab may boost immune cells to recognize and kill cancer cells that do not respond well to pembrolizumab alone. This could help more patients to get long-lasting benefits from this immunotherapy.
In earlier studies, efti was tested in combination with pembrolizumab. It was found to be well tolerated and safe in participants with another type of cancer. This study was phase 2, meaning that efti was tested in a small number of participants to assess its safety and to get some data on its effectiveness against the cancer.
The main objective of this TACTI-002 study is to find out how adding efti to pembrolizumab will impact the percentage of participants whose tumours noticeably shrink or disappear (called response) in those with metastatic NSCLC, PD-1/PD-L1 refractory NSCLC, or metastatic head and neck cancer.
In addition, this study tested:
• Whether the drug combination is safe and well handled by participants.
• How well the drug combination works together to fight cancer.
• How efti behaves in the body and if it causes any immune reactions.2. WHAT HAPPENED DURING THE STUDY?
A total of 189 participants were enrolled and divided into 3 parts:
• Part A: 114 participants
• Part B: 36 participants
• Part C: 39 participants
Details on who was included in each part is described in Section 4.
This study was “open-label”, meaning that participants and doctors knew what treatments participants were receiving. All participants were to receive pembrolizumab for up to 2 years and efti for up to 1 year. Participants were to be treated until their cancer stopped responding or got worse, until they developed unacceptable medical problems, or until they chose to stop treatment. During the first year, pembrolizumab was given with efti (combo-treatment). Afterwards, participants received pembrolizumab alone (monotherapy) for another 12 months. After the treatment ended, participants were followed until they chose to leave the study, the end of the study, or death, whichever came first.
3. WHEN AND WHERE DID THIS STUDY TAKE PLACE?
When was the study performed?
The study started on 18 February 2019 (first participant’s initial treatment) and ended on 25 November 2024 (last participant’s final visit).
Where did the study take place?
The study was conducted across 18 sites in 6 countries (Australia, Poland, Spain, Ukraine, United Kingdom and United States of America).
4. WHO PARTICIPATED IN THE STUDY?
What kind of participants were included in the study?
Potential participants were evaluated by the study doctors to make sure they met criteria to participate. The main selection criteria are listed below:
● Women or men who were 18 years or older.
● For Part A: had advanced or metastatic NSCLC that could not be removed with surgery or treated with drugs targeting specific mutations. They had not received any treatment for their advanced cancer before, except for radiotherapy to relieve symptoms.
● For Part B: had advanced or metastatic NSCLC that had stopped responding to the first treatment including PD-1 or PD-L1 immunotherapy, either alone or in combination with other types of immunotherapies or chemotherapy.
● For Part C: had Head and Neck cancer that had come back or spread and cannot be cured with surgery, radiation or other treatments. Or their cancer did not respond or came back after been treated with chemotherapy.
● Good overall health, no troubles with daily activities.
● Had a life expectancy of longer than 3 months.
● The tumour locations could be measured.These are just some of the criteria people had to meet to join the study. There were also other criteria that aren't listed here. You can find more information about all other results listed at the end of this summary.
What were the ages and genders of the participants who participated in the study?
A total of 189 participants joined this study. All participants were between the ages of 37 and 85 years. 141 of the 189, or 74.6% of participants were men. 48 of the 189, or 25.4% of the participants were female.5. WHAT TREATMENTS DID PARTICIPANTS RECEIVE?
Pembrolizumab (200 mg) was provided as a solution for injection into the vein (administered as a 30-minute infusion) every 3 weeks, for up to 2 years.
Efti (30 mg) was given as an injection under the skin of one thigh. Participants were injected every 2 weeks for the first 6 months, then every 3 weeks, for up to 1 year.6. WHAT WERE THE SIDE EFFECTS?
The researchers recorded any side effects participants had during the study. Side effects could happen for reasons not related to the study treatment (for example, caused by an underlying disease or by chance). Or, side effects could also have been caused by a study treatment, or by another medicine the participant was taking. Sometimes the cause of a side effect is unknown. By comparing side effects across many treatment groups in many studies, doctors try to understand what the side effects of an experimental drug might be.
In this study, side effects were unwanted events that might have possibly been caused by either or both of the study drugs (efti and/or pembrolizumab).What were the most common side effects?
The most common side effects caused by the study drugs that were reported are as follows;
Skin itchiness: 34 out of 189 (18%) participants
Weakness: 32 out of 189 (16.9%) participants
Underactive thyroid: 16 out of 189 (8.5%) participants These side effects are generally symptoms related to cancer.What is a serious side effect and how many of them occurred?
A side effect is serious when:
● The participant needs to be hospitalized or needs to stay in hospital for a longer period.
● The participant’s life is in danger.
● It causes permanent damage or death.
● It puts the participant at risk and requires the care of a doctor to prevent the situation mentioned above.
● It causes a birth defect.In this study, 18 participants (9.5%) experienced serious side effects possibly related to efti and/or pembrolizumab treatment. The most common serious side effect in Part A was lung inflammation, which occurred in 3 out of 114 participants (2.6%). In Part B and Part C, no serious side effects occurred in more than 1 participant.
How many deaths occurred during the study?
In this study, 3 deaths occurred in the study (all in Part A) due to side effects possibly related to efti and/or pembrolizumab treatment: (1) lung inflammation caused by the immune system, (2) blood clot in the lung, and (3) sudden death from an unknown cause.How many participants stopped treatment because of side effects?
In Part A, 10 out of 114 participants (8.8%) stopped treatment with efti/pembrolizumab because of side effects that were considered possibly related to the study drugs.
In Part B, participants did not stop treatment due to possibly related side effects.
In Part C, 2 out of 39 participants (5.1%) discontinued treatment early due to possibly related side effects.
You can find more information about all other side effects results listed at the end of this summary.7. WHAT WERE THE STUDY RESULTS?
What were the results of the study?
Researchers looked at the percentage of participants whose tumours shrank or disappeared with treatment—this is called the objective response rate (ORR) and was double-checked with follow-up scans. They also measured the duration of time that the tumours shrank or ceased growing. The point at which half of these participants were still experiencing this benefit is called the median duration of response (DoR). Additionally, they measured median overall survival (OS), which is how long half the participants stayed alive after they started treatment. A summary of the results is provided below.Part A (114 participants)
Confirmed ORR: 40 out of 114 participants (35.1%) Median DoR: 21.6 months Median OS: 22.6 monthsPart B (36 participants)
Confirmed ORR: 3 out of 36 participants (8.3%) Median DoR: 10.3 months Median OS: 9.9 monthsPart C (37 participants)
Confirmed ORR: 10 out of 37 participants (27.0%) Median DoR: 42.6 months Median OS: 8.7 months
Note: Two participants were excluded from Part C as they died due to COVID before having any scans.8. HOW HAS THE STUDY HELPED PARTICIPANTS AND RESEARCHERS?
This summary is based on a study that included 189 participants with advanced/metastatic NSCLC, PD-1/PD-L1 refractory NSCLC and recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). The results of this study helped researchers learn more about these types of cancers and how they respond to treatment with efti and pembrolizumab.
Overall, the treatment combination of efti and pembrolizumab was shown to be generally safe and well tolerated with no new common side effects identified.
Further research is required with a control arm to further test how well these treatments work in larger groups of participants.
One study alone can’t tell us everything about how safe or helpful a medicine is. We need many studies with lots of people to get the full picture.9. ARE THERE PLANS FOR FURTHER STUDIES?
Yes, a study has been set up to further investigate efti in participants with advanced or metastatic non-small cell lung cancer, where efti is given together with pembrolizumab and chemotherapy.
Another study has been conducted to evaluate how well and safe the combination of efti and pembrolizumab is compared with pembrolizumab alone in participants with recurrent or metastatic head and neck cancer.10. FURTHER INFORMATION
The full title of the study is: TACTI-002 (Two ACTive Immunotherapeutics): A multicenter, open label, Phase II study in patients with previously untreated unresectable or metastatic non-small cell lung cancer (NSCLC), or recurrent PD-X refractory NSCLC or with recurrent or metastatic squamous head and neck cancer (HNSCC) receiving the soluble LAG-3 fusion protein eftilagimod alpha (IMP321) in combination with pembrolizumab (PD-1 antagonist).What are the identification details of the clinical study?
Protocol Number: TACTI-002 (IMP321-P015); Keynote-PN798 EudraCT Number: 2018-001994-25 Clinicaltrials.gov Number: NCT03625323What is the name of the Sponsor of the study?
The company organizing and funding the research is called Immutep S.A.S., based in France.How can you contact the Sponsor of the study?
You can reach them on the Immutep website: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.immutep.com%252Fcontacts%252Fcontact.html.%2FNBTI%2FMYLBAQ%2FAQ%2F4fb97388-4848-4b92-a375-6ef55a67df36%2F2%2FLcOwWbd3u6&data=05%7C02%7Charrow.rec%40hra.nhs.uk%7Cabd71317aba74642650408de2847347b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638992483466189417%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=hcGAFRQz5%2B70hr3nn1VUVdwBVsNdCrzQ%2B%2BEMdTHA7j8%3D&reserved=0Where can you learn more about the study?
Further information is available at: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT03625323.%2FNBTI%2FMYLBAQ%2FAQ%2F4fb97388-4848-4b92-a375-6ef55a67df36%2F3%2F4OdPvyJ7EC&data=05%7C02%7Charrow.rec%40hra.nhs.uk%7Cabd71317aba74642650408de2847347b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638992483466210007%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=CeZypRPOsecZIpOWtdTjGFlVn0apGcfgeUbNJSnxw9w%3D&reserved=0REC name
London - Harrow Research Ethics Committee
REC reference
18/LO/1889
Date of REC Opinion
7 Feb 2019
REC opinion
Further Information Favourable Opinion