Phase 3 Trial of Perioperative EV and Pembro vs. Chemo in Cis-E MIBC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Apr 2021 → ongoing

Decision date (initial)

2023-12-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-505615-21-00

EudraCT number

2020-003106-31

WHO UTN

U1111-1292-1300

ClinicalTrials.gov

NCT04700124

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic, Safety, Others, Diagnosis, Efficacy

1. To compare event-free survival (EFS) in Arm A (perioperative EV + pembrolizumab and RC + PLND) versus Arm B (neoadjuvant gemcitabine + cisplatin and RC + PLND).

Secondary objectives 6

1. To compare pathologic complete response (pCR) rates obtained in Arm A (preoperative enfortumab vedotin [EV] + pembrolizumab and radical cystectomy [RC] + pelvic lymph node dissection [PLND]) versus Arm B (neoadjuvant gemcitabine + cisplatin and RC + PLND).
2. To compare overall survival (OS) in Arm A (perioperative EV + pembrolizumab & RC + PLND) versus Arm B (neoadjuvant gemcitabine + cisplatin & RC + PLND).
3. To assess disease-free survival (DFS) in Arm A (perioperative EV + pembrolizumab & RC + PLND) & Arm B (neoadjuvant gemcitabine + cisplatin & RC + PLND), participants who are disease free after surgery.
4. To assess the rate of pathologic downstaging (pDS) in Arm A (preoperative EV + pembrolizumab & RC + PLND) & Arm B (neoadjuvant gemcitabine + cisplatin & RC + PLND.
5. To evaluate safety & tolerability of perioperative EV + pembrolizumab + RC + PLND in Arm A.
6. To evaluate changes from baseline in health-related quality of life (HRQoL) & time to deterioration, using 2 general instruments (European Organization for Research & Treatment of Cancer [EORTC] QoL questionnaire-Core 30 [QLQ-C30], & European Quality of Life [EuroQoL]- 5 Dimensions, 5-level Questionnaire [EQ-5D-5L]), & 1 disease-specific instrument (Bladder Cancer Index [BCI]).

Conditions and MedDRA coding

Muscle Invasive Bladder Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology
2. Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis
3. Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)
4. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Have adequate organ function

Exclusion criteria 13

1. Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions
2. Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
3. Has ≥N2 disease or metastatic disease (M1) as identified by imaging
4. Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol
5. Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder
6. Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC
7. Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
8. Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection. Hepatitis B infection or known active Hepatitis C infection
9. Has a known psychiatric or substance abuse disorder
10. Has had an allogenic tissue/solid organ transplant
11. Has ongoing sensory or motor neuropathy Grade 2 or higher
12. Has active keratitis (superficial punctate keratitis) or corneal ulcerations
13. Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to <8% with associated diabetes symptoms

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event-Free Survival (EFS)

Secondary endpoints 15

1. Pathologic Complete Response (pCR) Rate
2. Overall Survival (OS)
3. Disease Free Survival (DFS)
4. Pathologic Downstaging (pDS) Rate
5. Number of Participants Who Experienced An Adverse Event (AE) (Arm A only)
6. Number of Participants Who Discontinued Study Treatment Due to An AE (Arm A only)
7. Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ- C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score
8. Change from Baseline in EORTC QLQ-C30 Physical Functioning Scale
9. Change from Baseline in Urinary, Bowel and Sexual Domains per Bladder Cancer Index (BCI)
10. Change from Baseline in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ- 5D-5L) Visual Analogue Score (VAS)
11. Time to Deterioration (TTD) in the EORTC-QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30)
12. TTD in the Physical Functioning Scale per EORTC QLQ-C30
13. TTD in the Role Functioning Scale per EORTC QLQ-C30
14. TTD in the Urinary, Bowel and Sexual Domains per BCI
15. TTD in the EQ-5D-5L VAS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Aljosja Rogiers

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Aljosja Rogiers

Third parties 5

Locations

12 EU/EEA countries · 66 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 97 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications