Registry Study to Evaluate Survival and Safety of T-VEC Subjects
Research type
Research Study
Full title
A Registry Study to Evaluate the Survival and Long-Term Safety of Subjects Who Previously Received Talimogene Laherparepvec in Amgen or BioVEX-Sponsored Clinical Trials
IRAS ID
236687
Contact name
Sophie Papa
Contact email
Sponsor organisation
Amgen Ltd
Eudract number
2015-003196-29
Clinicaltrials.gov Identifier
Duration of Study in the UK
5 years, 1 months, 23 days
Research summary
Research Summary
A registry study is to evaluate the overall survival, use of subsequent anti-cancer therapy, and the long-term safety of subjects who have received at least one dose of talimogene laherparepvec on an Amgen or BioVEX-sponsored clinical trial for any tumor type. Follow-Up will occur every 3 months.
Summary of Results
1. Study Name Title of the Study: A Registry Study to Evaluate the Survival and Long-Term Safety of Subjects Who Previously Received Talimogene Laherparepvec in Amgen or BioVEX-Sponsored Clinical Trials Brief Title: Registry Study for Talimogene Laherparepvec Protocol Number: 20120139 EU Trial Number: 2015-003196-29 Other Identifiers: NCT02173171 Date of This Summary: 09 September 2022 Before this registry study, 9 preceding clinical studies (here called “parent studies”) took place. At the end of the study treatment in each of these studies, participants were given the opportunity to enroll in the registry study and continue follow-up for long term monitoring of treatment-related side effects.
This summary shows the main results from the registry study and also includes some data from its preceding parent studies. The results are only for these studies.
Other studies may find different results. Researchers and health authorities look at the results of many studies to decide which medicines work best and are safest for patients.
Amgen has committed to make research results available to the public. This summary has been provided as part of that commitment and should not be used for any other purpose. It should not be considered to make a claim for any product or to guide treatment decisions.
Clinical Study Results
What does this summary cover?
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Some information in this summary may be different from the approved labelling for IMLYGIC® (talimogene laherparepvec). Your healthcare professional should refer to the full prescribing information for proper use of IMLYGIC®.
2. Who Sponsored This Study?
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799 USA
Phone (United States): +1 805-447-1000
Amgen Inc. is the sponsor of the study who made talimogene laherparepvec, the medicine tested in the study. Amgen and BioVEX sponsored this registry study and the preceding clinical studies (called “parent studies”).
Amgen would like to thank everyone who participated in this study and feels it is important to share the results of this study.
3. General Information About the Clinical Study • This registry study took place in Austria, Canada, France, Germany, Greece, Hungary, Italy, Poland, Republic of Korea, Russian Federation, South Africa, Spain, Switzerland, the United Kingdom, and the United States.
• The registry study began in April 2010 and ended in September 2021.
• The registry study was completed as per study plan.
Where and when was the study done?
3
This was an observational registry study, which means that no study treatments were administered to participants.
In one of the 9 earlier parent studies, each participant had received at least 1 dose of talimogene laherparepvec for various types of cancer, such as melanoma (a type of skin cancer). This observational study further followed the participants who had received talimogene laherparepvec in a parent study.
The purpose of this observational study was to monitor the occurrence of side effects over a longer period and to find out if participants were given any subsequent anti-cancer treatments. This was done by contacting the participants approximately every 3 months.
4. Who Was Included in This Study?
This study included 186 participants with various types of tumors. Participants in a parent study with any tumor type could be included, if they had received at least
1 dose of talimogene laherparepvec.
However, data from 8 participants was not used in these analyses (6 participants were still undergoing follow-up on their parent study and 2 participants had not received talimogene laherparepvec). Therefore, the data that was analyzed included
178 participants.
Eighty-three participants (47%) were women and 95 participants (53%) were men.
They ranged in age from 19 to 96 years. The average age was about 64 years;
146 participants (82%) were 50 years or older.
Why was the study done?
Who took part in the registry study?
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This study took place at 52 study centers across Austria, Canada, France, Germany, Greece, Hungary, Italy, Poland, Republic of Korea, Russian Federation, South Africa, Spain, Switzerland, the United Kingdom, and the United States. The numbers of participants in each country are listed in the table below:
Number of Participants per Country
United States 110 participants
Greece 11 participants
Russian Federation 11 participants
Spain 10 participants
Switzerland 10 participants
United Kingdom 8 participants
Canada 5 participants
France 5 participants
Italy 5 participants
Austria 3 participants
South Africa 3 participants
Republic of Korea 2 participants
Germany 1 participant
Hungary 1 participant
Poland 1 participant
Participants were chosen to be in the study if they received at least 1 dose of talimogene laherparepvec on an Amgen or BioVEX-sponsored clinical trial for any tumor type, but had since stopped treatment. The registry study analysis set included 178 participants and data from this group was used to analyze the side effects. An analysis set is a collection of data from a specific group of participants that is used to answer different questions of a clinical study.
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In addition to the data from the registry study, this study also looked at data long-term data from 2 other data sets to get as much insight as possible. Long-term follow-up means that a participant’s health and overall survival was monitored over a longer period. The longer observation period makes sure that late side effects are also noticed and documented. Not all parent studies included a long-term follow-up.
Long-term data could be collected from participants in a study which included a follow-up period, and also separately in the registry study.
These data sets are described below:
• For the analysis of related long-term side effects, this study also looked at the data from participants who participated in the long-term follow-up of one of the parent studies, but did not necessarily have data in registry study itself. This group included 1077 participants. Of these, 107 participants were both in the long-term follow-up of one of the parent studies and also in the registry analysis set, and hence provided data in the parent study as well as in the registry.
• For the analysis of side effects and overall survival, participant data from a post-treatment analysis set was looked at. The post-treatment analysis set included 1148 unique participants with various types of tumors who took part in the long-term follow-up of a parent study and/or the registry study.
Participants with any tumor type eligible for treatment with talimogene laherparepvec could be included. In the post-treatment analysis set,
498 participants (43%) were women and 650 (57%) were men. They ranged in age from 11 to 96 years. The average age was about 63 years.
What other data was analyzed?
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5. Which Medicines Were Studied?
Talimogene laherparepvec is a modified herpes simplex virus type-1 (similar to the ‘cold sore’ virus). The virus’ genes were modified in a laboratory to make the virus active in tumor cells but not in normal cells. This modified virus is not designed to change any of the participant’s genes, but is designed to infect tumor cells and cause a release of proteins that are specific to the tumor to stimulate the immune system to respond against the cancer.
Talimogene laherparepvec is intended to work in 2 ways:
• by directly destroying cells in the treated tumors themselves, and • by making the participant’s own immune system more active in destroying tumor cells throughout the body, not just where it is injected.
This observational study further followed the participants who had received talimogene laherparepvec in an earlier parent study. No treatments were administered to participants during this observational registry study. The purpose was to monitor the occurrence of side effects over a longer period after the treatment and to find out if participants were given any subsequent anti-cancer treatments.
6. What Were the Side Effects?
All medicines can cause side effects, or unwanted medical problems that may happen when you take a medicine. For this study, the investigators reported side effects they considered to be related to talimogene laherparepvec. These possible side effects are described below.
What is a side effect?
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The table below shows how many participants had side effects.
Side Effects During the Study
Post-treatment
Analysis Set
(1148 unique
participants)
Data From the
Registry Study
Analysis Set
Only
(178 participants)
Data From
Post‑treatment
Long-Term
Follow-up in a
Parent Study Only
(1077 participants)
How many
participants had
serious side effects?
10 participants (1%) 1 participant (1%) 9 participants (1%) How many participants had nonserious side effects?
99 participants (9%) 2 participants (1%) 97 participants (9%) How many participants died from side effects?
1 participant (< 1%) 0 participants (0%) 1 participant (< 1%) Side effects can be classified as serious and non-serious. If a participant experienced a side effect that was classified as serious (including, for example, if a participant had to stay in the hospital or died because of a side effect), the doctor was to report that the side effect was serious.
No participant died due to a side effect in the registry study. One participant in the post-treatment analysis set died due to an inflammatory reaction causing the release of proteins called cytokines and a buildup of fluid in the space that surrounds the lungs.
Ten participants (1%) in the post-treatment analysis set had a serious side effect, of which one (a serious complication of diabetes resulting in the breakdown of the
metabolism) was reported in a participant in the registry study. The remaining
9 occurred in participants in the long-term follow-up of one of the parent studies.
No serious side effect occurred in more than 1 participant.
What side effects were seen?
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The table below shows the reported serious side effects.
Serious Side Effects During the Study
Serious side effect
Post-treatment
Analysis Set
(1148 unique
participants)
Data From the
Registry Study
Analysis Set
Only
(178 participants)
Data From
Post‑treatment
Long-Term
Follow-up in a
Parent Study Only
(1077 participants)
Inflammatory reaction
causing the release of
proteins called cytokines
1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Inflammation of the
innermost layer of skin
1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Breakdown of the
metabolism due to
diabetes
1 participant
(< 1%)
1 participant
(1%)
0 participants
(0%)
Blood in stools 1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Impaired wound healing 1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Skin cancer that has
spread to other parts of
the body
1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Nervous system disorder 1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Nerve damage in arms or
legs
1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Fluid on the lungs 1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Inflammation of lung
tissue
1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Fever caused by cancer 1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Increased growth of a
cancer
1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
Wound 1 participant
(< 1%)
0 participants
(0%)
1 participant
(< 1%)
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The table below shows the reported non-serious side effects that occurred in at least 0.5% of participants (or about 5 out of 1000) in any group.
Non-serious Side Effects During the Study Non-serious side effect Post-treatment Analysis Set
(1148 unique
participants)
Data From the
Registry Study
Analysis Set
Only
(178 participants)
Data From
Post‑treatment
Long-Term
Follow-up in a
Parent Study Only
(1077 participants)
Rash 9 participants
(0.8%)
0 participants
(0.0%)
9 participants
(0.8%)
Patches of the skin
losing their pigment
9 participants
(0.8%)
0 participants
(0.0%)
9 participants
(0.8%)
Being very tired 8 participants
(0.7%)
0 participants
(0.0%)
8 participants
(0.7%)
Itching 7 participants
(0.6%)
0 participants
(0.0%)
7 participants
(0.6%)
Pain in a joint 6 participants
(0.5%)
0 participants
(0.0%)
6 participants
(0.6%)
Increased liver
enzyme (ALT)
5 participants
(0.4%)
0 participants
(0.0%)
5 participants
(0.5%)
Loose stools 5 participants
(0.4%)
0 participants
(0.0%)
5 participants
(0.5%)
Cold sores (oral
herpes)
5 participants
(0.4%)
0 participants
(0.0%)
5 participants
(0.5%)
Flat and raised red
skin rash
5 participants
(0.4%)
0 participants
(0.0%)
5 participants
(0.5%)
This section only shows the most often reported side effects considered by the study doctor as related to study medicine. No single study can give a complete picture of the benefits and risks of a medicine. Information about other side effects may be available at the websites listed at the end of this summary.
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7. What Were the Overall Results of the Study?
The main intentions of this study were:
• to see the long-term safety of talimogene laherparepvec, • to measure the survival of cancer patients receiving it, and • to assess subsequent anti-cancer therapy in participants who received at least
1 dose of talimogene laherparepvec in a parent study.
In the registry study, participants were followed between 0 and 136 months after the treatment; the median duration (the median is the middle number in a list of numbers arranged in order: half the values were lower and half were higher than the median
value) was 34 months. Participants in the post-treatment analysis set were followed between 0 and 92 months, with a median of 15 months.
Of the 178 participants in the registry study analysis set, 1 participant (1%) reported a serious side effect and 2 participants (1%) reported non-serious side effects during the registry study.
No long-term safety concerns for talimogene laherparepvec were identified.
The overall survival is the time from when a participant received the first dose of talimogene laherparepvec in the parent study to the time a participant died from any cause either in a parent study or in the registry study.
At the time of this analysis, half of the participants in the post-treatment analysis set
(571 out of 1148 participants, 50%) had died.
The median survival time in the post-treatment analysis set was 4 years.
How long were participants in the study before they died or the study ended?
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In both analysis sets, 38% of participants received subsequent anti-cancer therapies.
The most commonly reported therapies are shown in the below table.
Participants Receiving Subsequent Anti-cancer Therapies Subsequent anti-cancer therapies Post-treatment Analysis Set
(1148 unique participants)
Registry Study
Analysis Set
(178 participants)
Any drug 436 participants (38%) 67 participants (38%) Pembrolizumab 99 participants (9%) 38 participants (21%) Nivolumab 81 participants (7%) 23 participants (13%) Ipilimumab 78 participants (7%) 19 participants (11%) Dabrafenib 50 participants (4%) 10 participants (6%) Trametinib 40 participants (4%) 11 participants (6%) Other drugs Less than 5% of participants per therapy Less than 5% of participants per therapy More results may be available at the websites listed at the end of this summary.
8. How Has This Study Helped Participants and Researchers?
This study may help future patients and families by helping doctors understand more about the medicine in this study. This study helped researchers understand if any side effects occurred after the treatment concluded, how participants carried on after treatment, and what kind of treatments they required later.
What else is important to know about these results?
These results are only for a sample of 1148 unique participants (post-treatment analysis set) which include information from 178 participants in the registry study and from 1077 participants in the long-term follow up of a parent study. Not all What kind of anti-cancer drugs did participants receive after treatment with talimogene laherparepvec?
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participants in the described studies had the same results. The results for any single participant could have been better or worse than the results for their group. Other studies may find different results. These results do not explain how a study medicine may work in a single person. Many studies are needed to show the benefits and risks of a medicine that is still being tested. This research may help future participants and families by helping doctors understand more about the study medicine being studied.
9. Are There Plans for Further Studies?
If more clinical studies are done, they may be listed on public websites, such as those below. Search for study medicine name talimogene laherparepvec or IMLYGIC® on the websites below.
10. Where Can I Find More Information About This Study?
To find out more about this study, check these websites:
• https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cdf947ead14744323d22f08da9d6bf358%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637995384228940728%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=%2FmUcq8gadzxMSjQFWzvFBy2dCjeu2rRxd%2BAxJkMgjMA%3D&reserved=0. Use the study identifier 2015-003196-29.
• https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cdf947ead14744323d22f08da9d6bf358%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637995384228940728%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=KQ0DJnotVtvNWe4doQ6tLvSvdiWOjj8B7kBpy%2Fo6xOY%3D&reserved=0. Use the study identifier NCT02173171.
If you participated in the study and have questions about the study results, the doctor or staff at your study center may be able to answer them.REC name
North East - York Research Ethics Committee
REC reference
18/NE/0005
Date of REC Opinion
7 Feb 2018
REC opinion
Further Information Favourable Opinion