Activity and Safety of Danvatirsen and Pembrolizumab inHNSCC
Research type
Research Study
Full title
An Open-Label, Phase II, Randomized, Controlled Study of Danvatirsen Plus Pembrolizumab Compared to Pembrolizumab Alone in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
IRAS ID
1009267
Contact name
Susan Macintyre
Contact email
Sponsor organisation
Flamingo Therapeutics
Clinicaltrials.gov Identifier
Research summary
Summary of Research
Head and neck cancer is the sixth most common cancer worldwide. Despite the strong medications available for patients when they are first treated, a significant percentage of patients will have a relapse of their head and neck cancer or it will spread to other parts of their body known as metastasis . Keytruda© is a therapy approved for the treatment of head and neck cancer that has relapsed or metastasised. This study will evaluate if the combination of Keytruda with an investigational agent, danvatirsen, will be a more effective treatment than Keytruda alone.Persons who are 18 years of age or older with relapsed or metastasised head and neck cancer who want to participate in the study, will have a series of evaluations to determine if they are eligible to enroll and receive medication. Persons who are eligible to enroll in the study, will be randomly assigned to receive either danvatirsen + Keytruda or Keytruda alone. Participants who receive the investigational drug, will have an intravenous (IV) infusion of danvatirsen followed by an IV infusion of pembrolizumab every week. Participants receiving Keytruda alone will have an IV infusion of Keytruda every 3 weeks. All participants will continue study medication until the medication is no longer effective or they have intolerable side effects or they reach the maximum amount allowed. During treatment a participant will have assessments regularly performed such as physical exams, blood levels, scans of their tumors and other procedures. After a participant discontinues from the medication, they continue to have visits and contact with their study doctor to monitor their health.
This study is being funded by Flamingo Therapeutics and will be conducted at multiple location globally. This study will be overseen by a safety review committee to ensure the safety of study participants.
Summary of Results
Summary of the study and its results:
The above reference trial was sponsored by Flamingo Therapeutic BV. Approval to conduct the trial was received by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and London - Fulham Research Ethics Committee (REC) which included review and input by the Patient and Public Involvement and Engagement Group at the Royal Marsden. Flamingo Therapeutics would like to thank the participants and their families for participating in the trial.
This study included 66 participants with Head and Neck Cancer (Head and Neck Squamous Cell Carcinoma (HNSCC)), specifically cancer that has spread beyond the head and neck location (metastatic) or has come back (recurrent) after previous treatment for disease located only in the head and neck region. Metastatic participants had to not have been previously treated for their metastatic Head and Neck Cancer. Participants in the trial were from one of 3 countries (UK, US and South Korea) aged ≥18 years and were positive for a marker on the cells of their tumor. This marker is known as PD-L1, and positive PD-L1 expression in tumor was determined by a test on tissue from the tumor with a positive test result defined as a combined positive score (CPS) ≥1. Participants were randomly assigned in a ratio of 2 to 1 to receive an investigational new drug, (danvatirsen 3 mg/kg IV weekly) in combination with the approved therapy Keytruda, (pembrolizumab 200 mg IV every 3 weeks) or Keytruda 200 mg IV every 3 weeks alone. Keytruda 200 mg IV every 3 weeks alone is an approved treatment for these participants and considered one possible standard of care. The purpose of the study was to determine if the combination of danvatirsen plus pembrolizumab was more effective in treating participants’ cancer than pembrolizumab therapy alone and to study the side effects of the treatment. Participants received 21-day treatment cycles until their cancer progressed, or they had unacceptable side effects, or voluntary withdrawal.
An interim analysis of the participant’s response to treatment was conducted and it showed the combination danvatirsen plus Keytruda did not appear to improve outcomes compared to Keytruda alone in the designated participant population. Thus, danvatirsen did not provide any added benefit.
As a result of this analysis, enrollment into the trial was stopped and the participants that were currently receiving the combination of danvatirsen and Keytruda were transitioned to another therapy for their HNSCC, which may have been Keytruda alone.
The most common side effects in participants in the trial were liver enzyme elevations, low red blood cells, fatigue, low platelets, nausea, diarrhea, constipation.
After collection of all remaining data, a final analysis was conducted which confirmed that danvatirsen plus pembrolizumab did not more effectively treat HNSCC compared to pembrolizumab alone. Additional study data will be available on the website Clinicaltrials.gov under NCT05814666.REC name
London - Fulham Research Ethics Committee
REC reference
24/LO/0144
Date of REC Opinion
9 Apr 2024
REC opinion
Further Information Favourable Opinion