GSK 213152, Bintrafusp Alfa in patients with Urothelial Cancer
Research type
Research Study
Full title
A Phase Ib Trial to Evaluate the Efficacy and Safety of Bintrafusp Alfa Monotherapy in Metastatic or Locally Advanced/Unresectable Urothelial Cancer with Disease Progression or Recurrence Following Treatment with a Platinum Agent
IRAS ID
280988
Contact name
Thomas Powles
Contact email
Sponsor organisation
GlaxoSmithKline Research & Development Limited
Eudract number
2020-000416-29
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
145828, IND
Duration of Study in the UK
1 years, 11 months, 16 days
Research summary
Research Summary
This is a Phase Ib open label, single arm study of bintrafusp alfa, the study drug, in participants with bladder (urothelial) cancer that has spread or cannot be removed by surgery.
Bintrafusp alfa is intended to help the body’s immune system act against cancer. It’s hoped that bintrafusp alfa may prevent cancer cells from growing. Bintrafusp alfa has been tested in more than 600 patients with different cancers, including patients with non-small cell lung cancer (NSCLC) and biliary tract cancer (BTC), but it has not been tested in patients with bladder (urothelial) cancer.
This study has 3 study periods; Screening (up to 6 weeks), Treatment (until complete response or disease progression), and Follow-Up (12 weeks plus long-term follow-up every 12 weeks until death or end of study).
All participants in the study will receive the study drug. The study drug will be given as a drip into a vein (intravenous (IV) infusion) once every 2 weeks at a dose of 1200mg. The infusion will take about 1 hour. Participants will receive treatment for up to 2 years after the Complete Response is confirmed (responded well to study drug), until their cancer worsens (disease progression) or withdrawal from the study for another reason.
The primary objective is to evaluate the anti-tumour activity (prevention or inhibition of formation or growth of tumours) in participants with bladder cancer treated with bintrafusp alfa. Secondary objectives include evaluation of other measures of antitumor activity, evaluation of effectiveness based on Overall Survival and evaluation of safety and tolerability of bintrafusp alfa.
The study will comprise of approximately 15 sites globally, including North America and Europe, and plans to enrol approximately 40 eligible participants.
Summary of Results
This was a Phase Ib clinical study, designed to assess the efficacy and safety of Bintrafusp Alfa monotherapy in metastatic or locally advanced/unresectable urothelial cancer with disease progressions or recurrence following treatment with a platinum agent. Study 213152 was designed as an open-label global multicenter single-arm study. A total of 37 participants were screened; of those, 25 participants were enrolled and treated. The median duration of treatment was 8 weeks. Twelve participants died during the study, mostly due to the disease under study. The enrollment into the study was stopped early based on a review of available clinical activity data from the study which indicated that Bintrafusp Alfa was unlikely to show benefit beyond current available therapies. No new safety signals were identified.
Overall, treatment with Bintrafusp Alfa was well-tolerated and did not lead to any substantial or new safety concerns.
All participants in this study experienced TEAEs. The TEAEs occurring in the highest number of participants (≥25%) were anemia, constipation, and pruritus. Sixty-eight percent of participants experienced TEAEs related to Bintrafusp Alfa. Treatment-related TEAEs occurring in the highest number of participants (≥10%) included pruritus, anemia, fatigue, diarrhea, mucosal inflammation, dry mouth, nausea, and rash maculo-papular.
TEAEs of Grade ≥3 in severity occurred in 72% of participants. Sixty-eight percent of participants experienced serious TEAEs; most serious TEAEs occurred in 1 participant each. From serious TEAEs, urinal tract infection was reported in 4 (16%) participants, and pyrexia was reported in 2 (8%) participants.
From 12 participants who died during the study, 2 participants died due to fatal TEAEs (general physical health deterioration and septic shock) but none of those TEAEs were related to the study drug. Most participants who died during the study, died due to PD or disease related condition (9 participants).
No clinically important pattern was observed for AESIs or laboratory evaluations.
Two participants experienced infusion-related reactions. One participant experienced Grade 1 chills leading to temporary infusion interruption, and 1 participant experienced Grade 2 back pain and Grade 1 chills leading to infusion rate reduction/temporary interruption.
The BOR were confirmed CR in 2 (8%) participants, confirmed PR in 3 (12%) participants, PD in 13 (52%) participants, SD in 3 (12%) participants, and 4 (16%) participants were not evaluable. The ORR was 20% (95% CI [6.83, 40.70]).
Limited data collected and analyzed in this study do not allow making a definitive overall conclusion about the potential anticancer activity of Bintrafusp Alfa.REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
20/WM/0199
Date of REC Opinion
21 Aug 2020
REC opinion
Further Information Favourable Opinion