cetrelimab (JNJ-63723283)

P3, N=1135, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

P1, N=96, Recruiting, Johnson & Johnson Enterprise Innovation Inc. | N=66 --> 96

P1, N=200, Recruiting, Janssen Research & Development, LLC | N=345 --> 200

P2, N=160, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Dec 2026 --> Feb 2025

P3, N=518, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

P2, N=90, Recruiting, Spanish Oncology Genito-Urinary Group

SunRISe-1 (NCT04640623) is an ongoing randomized, phase 2b study assessing efficacy and safety of TAR-200 + cetrelimab (CET) (anti-PD1) (Cohort 1 [C1]), TAR-200 alone (C2), or CET alone (C3) in pts with BCG-unresponsive high-risk (HR) NMIBC with carcinoma in situ (CIS), with or without papillary disease, who are ineligible for or refusing radical cystectomy. In this study of SunRISe-1 PD-L1 expression limited by small sample size and number of clinical events, we observed high clinical response to TAR-200 monotherapy in HR NMIBC pts with BCG-unresponsive CIS irrespective of PD-L1 status.

P2, N=220, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

P1, N=345, Recruiting, Janssen Research & Development, LLC | Trial completion date: Mar 2026 --> Sep 2027

P1, N=345, Recruiting, Janssen Research & Development, LLC | N=20 --> 345

P2, N=120, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P2, N=2, Active, not recruiting, Rahul Aggarwal | Trial completion date: Feb 2026 --> Feb 2025 | Trial primary completion date: Feb 2025 --> Mar 2024

P3, N=1050, Recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2030 --> Sep 2029

P1, N=66, Recruiting, Johnson & Johnson Enterprise Innovation Inc. | Not yet recruiting --> Recruiting

P3, N=1050, Recruiting, Janssen Research & Development, LLC | Trial completion date: May 2030 --> Sep 2030

P1/2, N=80, Recruiting, Janssen Research & Development, LLC | Trial completion date: Nov 2025 --> Aug 2026

P1, N=66, Not yet recruiting, Johnson & Johnson Enterprise Innovation Inc.

P2, N=160, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Dec 2023 --> Dec 2026

P3, N=1050, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: May 2030 --> Sep 2029

P1/2, N=125, Active, not recruiting, Janssen Research & Development, LLC | Phase classification: P1b --> P1/2 | Trial completion date: May 2024 --> Jun 2025

P1/2, N=80, Recruiting, Janssen Research & Development, LLC | N=20 --> 80

P2, N=200, Recruiting, Janssen Research & Development, LLC | Phase classification: P2b --> P2

P1, N=20, Recruiting, Janssen Research & Development, LLC | Phase classification: P1b --> P1

P1/2, N=136, Active, not recruiting, Janssen Research & Development, LLC | Phase classification: P1b --> P1/2

P1, N=76, Recruiting, Johnson & Johnson Enterprise Innovation Inc. | Not yet recruiting --> Recruiting

P3, N=550, Recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2028 --> Dec 2029

P1, N=76, Not yet recruiting, Johnson & Johnson Enterprise Innovation Inc.

P2, N=160, Recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2025 --> Mar 2027

P2, N=2, Active, not recruiting, Rahul Aggarwal | Recruiting --> Active, not recruiting | N=24 --> 2 | Trial completion date: May 2026 --> Feb 2026 | Trial primary completion date: May 2025 --> Feb 2025

P2b, P3 | "Secondary end points include overall complete response rate (CIS only), recurrence-free survival, time to progression, overall survival, cancer-specific survival, safety, and pt-reported outcomes. As of May 3, 2023, 1 pt has been randomized, with 16 in screening; recruitment is planned at 254 sites."

P1/2, N=413, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | N=600 --> 413

P1/2, N=20, Recruiting, Janssen Research & Development, LLC

This activity is supported by educational grants from Astellas and Seagen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Gilead Sciences Inc, and Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC. Selection of patients with high-risk non-muscle-invasive bladder cancer (NMIBC) for pembrolizumab therapy Ongoing Phase III trials investigating the combination of BCG and anti-PD-1/PD-L1 antibodies for BCG-naïve and BCG-unresponsive NMIBC Rates of pathologic complete response and other clinically relevant endpoints achieved in early trials evaluating neoadjuvant anti-PD-1/PD-L1 antibody therapy for resectable muscle-invasive bladder cancer (MIBC) Key efficacy and safety data from the Phase III CheckMate 274 trial comparing nivolumab to placebo after radical surgery for high-risk MIBC Optimal integration of adjuvant nivolumab into clinical practice and identification of appropriate candidates Ongoing Phase III studies evaluating anti-PD-1/PD-L1 antibodies combined with chemotherapy, chemoradiation therapy, other immune checkpoint inhibitors or targeted therapies for patients with MIBC Mechanism of antitumor activity of and early data with the novel intravesical drug delivery system TAR-200 Design, eligibility criteria and key endpoints of the Phase II SunRISe-1 study evaluating TAR-200 and cetrelimab, TAR-200 alone or cetrelimab alone for patients with BCG-unresponsive high-risk NMIBC who are ineligible for or decline radical cystectomy; complete response rates reported with TAR-200 monotherapy and cetrelimab monotherapy Ongoing studies of TAR-200 with and without cetrelimab for NMIBC (eg, SunRISe-3) and MIBC (eg, SunRISe-2, SunRISe-4)

P2, N=160, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Apr 2023 --> Dec 2023

P1b, N=20, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting | N=40 --> 20

Background: First-line (1L) therapy for cisplatin (cis)-ineligible pts with mUC remains an unmet need and includes alternative chemotherapy or anti-PD-(L)1 monotherapy for PD-L1 positive tumors. Combination ERDA+CET demonstrated clinically meaningful activity and was well tolerated. These results, in 1L cis-ineligible pts, support previously described activity of ERDA monotherapy in FGFRa mUC. The safety profile was consistent with the known profile for ERDA and CET with no additive toxicity for the combination.

CME Provider and Supporter(s): This event is organized and accredited by Research to Practice and supported through educational grants provided by Astellas and Seagen Inc, AstraZeneca Pharmaceuticals LP, Gilead Sciences Inc, and Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC. Current clinical role of atezolizumab or pembrolizumab as first-line treatment for mUBC; importance of chemotherapy eligibility and PD-L1 status in patient selection for this strategy Appropriate incorporation of maintenance avelumab after front-line chemotherapy for mUBC Biologic rationale for the investigation of anti-PD-1/PD-L1 antibodies in combination with novel therapies (eg, enfortumab vedotin, erdafitinib) for previously untreated mUBC Recently presented efficacy and safety results from cohort K of the EV-103/KEYNOTE-869 study of first-line pembrolizumab in combination with enfortumab vedotin Potential clinical role of up-front pembrolizumab/enfortumab vedotin for patients with mUBC who are ineligible to receive cisplatin-based chemotherapy Preliminary data with erdafitinib in combination with cetrelimab for patients with previously untreated mUBC with FGFR3 or FGFR2 genetic alterations

TAR-200 was generally safe, well tolerated, and demonstrated preliminary efficacy in this elderly and frail cohort with limited treatment options. TAR-200 is currently under investigation in combination with the systemic inhibitor of programmed cell death protein-1 cetrelimab in the SunRISe clinical trials program (NCT04640623, NCT04658862, NCT04919512).

Ongoing and planned studies evaluating other novel approaches (eg, enfortumab vedotin, erdafitinib, nadofaragene firadenovec) for BCG-unresponsive NMIBC MODULE 2: The Role of Immune Checkpoint Inhibitors as Adjuvant and Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer (MIBC)rnrn1...Recent FDA approval of adjuvant nivolumab and identification of appropriate candidates for treatment 4...Current role of atezolizumab and pembrolizumab as first-line treatment for mUBC, importance of chemotherapy eligibility and PD-L1 status in selecting patients for this strategy 2. Key efficacy and safety data with maintenance avelumab after front-line chemotherapy for mUBC, appropriate incorporation into patient care 3...Preliminary data from the Phase I/II NORSE study of erdafitinib in combination with the investigational anti-PD-1 antibody cetrelimab for patients with previously untreated mUBC with FGFR3 or FGFR2 genetic alterations who are not eligible for cisplatin MODULE 4: The Selection and Sequencing of Therapy for Relapsed/Refractory mUBC 1...Emerging results from cohort 3 of the TROPHY U-01 trial combining sacituzumab govitecan and pembrolizumab 4...Optimal integration of enfortumab vedotin, sacituzumab govitecan and erdafitinib into therapy for progressive mUBCrnIncidence, severity and management of adverse events reported with enfortumab vedotin, sacituzumab govitecan or erdafitinib 6. Frequency of HER2 expression in UBC, mechanism of action of disitamab vedotin and available data and ongoing evaluation for patients with HER2-positive disease 7. Other promising agents and strategies under investigation for mUBC (eg, trastuzumab deruxtecan, futibatinib, infigratinib, cabozantinib) Target Audience This activity has been designed to meet the educational needs of medical and radiation oncologists, urologists and other allied healthcare professionals involved in the treatment of bladder cancer...RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose. Supporters This activity is supported by educational grants from Astellas and Seagen Inc, AstraZeneca Pharmaceuticals LP, Gilead Sciences Inc, and Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC.

The RP2D for cetrelimab was established. Pharmacokinetic/pharmacodynamic characteristics, safety profile, and clinical activity of cetrelimab in immune-sensitive advanced cancers were consistent with known PD-1 inhibitors.

GemRIS is an implantable novel form of intravesical drug delivery of gemcitabine and is currently being investigated with cetrelimab, a checkpoint inhibitor, in patients with high-risk NMIBC and MIBC...Nadofaragene firadenovec (rAd-IFN-α/Syn3) is a recombinant adenovirus that induces release of interferon-alpha in the urothelium...N-803 is an interleukin (IL)-15 analogue, which has been investigated in a phase 1b study in combination with BCG and has shown durable complete response in all nine patients for 72 months. It was granted breakthrough designation status by the FDA in 2019.

P2, N=24, Recruiting, Rahul Aggarwal | Not yet recruiting --> Recruiting