Substudy 04B: Phase 1/2 Umbrella Study in Urothelial Carcinoma

• Research type

  Research Study

• Full title

  A Phase 1/2 Randomized, Umbrella Study to Evaluate the Safety and Efficacy of Pembrolizumab Plus Enfortumab Vedotin (EV) in Combination With Investigational Agents Versus Pembrolizumab Plus EV, as First-Line Treatment for Participants With Advanced Urothelial Carcinoma (KEYMAKER-U04): Substudy 04B

• IRAS ID

  1006754

• Contact name

  - -

• Contact email

  N/A

• Sponsor organisation

  Merck Sharp & Dohme (UK) Limited

• Eudract number

  2022-001371-14

• Research summary

  Despite extensive clinical research and promising drug combinations being evaluated, locally advanced/metastatic urothelial cancer (la/mUC) is a serious and incurable condition with poor long-term survival and a high unmet medical need.

  This trial is testing 3 different trial drug combinations. All the drug combinations in this trial are experimental.

  Arm A: Enfortumab vedotin (EV) plus MK-4280A (MK-4280A is a combination of MK-4280 and pembrolizumab [pembro])
  Arm B: EV plus MK-7684A (MK-7684A is a combination of MK-7684 and pembro.)
  Arm C: EV plus pembro

  This substudy consists of 2 parts (approximately 390 participants):
  • Part 1 (base) will enrol 120 participants (approximately 40 per Arm)
  • Part 2 (expansion) will be conducted based on Part 1 results. Part 2 will enrol an additional 90 participants per Arm, on the Arm(s) selected for expansion (Arm A and/or Arm B and Arm C).

  There is a screening phase to see if participants can join the trial, lasting about one month.
  Eligible participants will be randomised in a 1:1:1 ratio into each Arm.

  Pembro, MK-4280A and MK-7684A will be given once every 3 weeks (Q3W) for about 2 years (35 cycles). EV will be given on 2 days Q3W as long as the cancer is not getting worse and there are no serious side effects.

  During the trial, participants will undergo procedures such as physical examinations, ECGs, blood/urine samples and scans. After the participants stop getting the trial drugs, they will enter the follow-up phase.

  The Sponsor estimates that the trial will require approximately 4 years per treatment arm from the time the first participant agrees to take part until the last trial related contact.

  The trial is sponsored by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (MSD).

• REC name

  London - Chelsea Research Ethics Committee

• REC reference

  23/LO/0077

• Date of REC Opinion

  17 Aug 2023

• REC opinion

  Further Information Favourable Opinion