Activity of Pembrolizumab plus Enfortumab Vedotin in Collecting Duct and Renal Medullary Carcinoma (REPRINT trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS Istituto Nazionale Dei Tumori

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-02-12

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Fondazione IRCCS Istituto Nazionale dei Tumori

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To evaluate activity of the combination Enfortumab Vedotin plus Pembrolizumab in terms of ORR.

Secondary objectives 2

1. to evaluate progression-free survival (PFS) and overall-survival (OS)
2. to evaluate tolerability

Conditions and MedDRA coding

Medullary Renal cell Carcinoma

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of metastatic or advanced Collecting Duct Carcinoma or Medullary Renal Cell Carcinoma will be enrolled in this study.
2. Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening. Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to treatment allocation. Hepatitis C screening tests are not required unless: • Known history of HCV infection • As mandated by local health authority
3. HIV-infected participants must have well-controlled HIV on ART. Please refer to the study protocol for the full text.
4. The participant provides written informed consent for the trial.
5. Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
6. Have confirmed histology diagnosis of Collecting Duct Carcinoma or Medullary Renal Cell Carcinoma by central pathology review.
7. Archival tumor tissue sample or newly obtained [core, incisional or excisional] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
9. Have adequate organ function as defined in the following table (Table 4). Specimens must be collected within 10 days prior to the start of study intervention.
10. Participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to treatment allocation. Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests are not required unless: • Known history of HBV infection • As mandated by local health authority

Exclusion criteria 19

1. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
2. Females who are pregnant, breastfeeding, or planning to conceive a child during the study duration (from screening through 12 months after the last dose of trial treatment) are excluded. Additionally, male participants who plan to father a child during treatment or within 9 months after the last dose of trial treatment are also excluded.
3. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid)
4. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
5. Has an active infection requiring systemic therapy.
6. Has not adequately recovered from major surgery or has ongoing surgical complications.
7. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
8. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
9. Has had an allogenic tissue/solid organ transplant.
10. Has received prior systemic anti-cancer therapy, including investigational agents, within 2 weeks prior to treatment allocation.
11. Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS diseases permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
12. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
13. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
14. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
15. Known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA <10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
16. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
17. Has a history of hypersensitivity reaction to Enfortumab Vedotin active substance and/or to any of the excipients.
18. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
19. Incapacitated participants - as not all requirements set in Article 31 of Reg EU 536/2014 are met, especially letter (e).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary Efficacy Endpoint is Objective Response Rate (ORR)

Secondary endpoints 1

1. The secondary endpoints of this study are progression-free survival (PFS), overall-survival (OS) and tolerability.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Istituto Nazionale Dei Tumori

Sponsor organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Address

Via Giacomo Venezian 1

City

Milan

Postcode

20133

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Giuseppe Procopio

Public contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Giuseppe Procopio

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 8 files

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

Application history

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