(UroToday.com) The 2024 Southern California Genitourinary Cancer Research Forum featured a bladder cancer session and a panel discussion of bladder cancer studies for NMIBC, MIBC, metastatic first-line, and metastatic salvage. Moderator Sia Daneshmand started by highlighting several important trials in the NMIBC disease space:
The first trial discussed by the panel was the SunRISe-1 trial, accruing patients at USC. The primary endpoint for this trial is complete response, and the secondary endpoints are duration of response, overall survival, adverse events, quality of life, and concentration of gemcitabine. The trial design is as follows:
The second trial in this disease space discussed by the panel is the ADVANCED-1 phase Ib trial (accruing at USC) assessing 18 patients undergoing TARA-002. The primary outcomes are maximal tolerated dose, dose limiting adverse events, dose limiting toxicity, and recommended phase 2 dose. The trial design for this trial is as follows:
The next trial was the PIVOT-006 trial assessing cretostimogene induction following TURBT + quarterly maintenance versus observation for IR-NMIBC, with patients being accrued at USC for this trial. The primary endpoint for PIVOT-006 is recurrence free survival (time frame of 51 months), and secondary endpoints are recurrence free survival and adverse events at 12 and 24 months). The trial design as follows:
The next trial discussed by the panel was the Johns Hopkins led phase 3 BRIDGE trial, accruing patients at UC San Diego. This trial is randomizing patients with treatment naïve histologically confirmed NMIBC to gemcitabine + docetaxel versus intravesical BCG with extended maintenance. The primary outcome for BRIDGE is event free survival, and the secondary outcomes are quality of life, cystectomy free survival, and progression free survival. The trial design for BRIDGE is as follows:
The final trial in the NMIBC space discussed by the panel is the KEYNOTE-057 trial, accruing at UCLA, which is selecting BCG unresponsive patients for Cohort A (pembrolizumab for up to 24 months for CIS +/- papillary tumors) or Cohort B (pembrolizumab for up to 24 months for papillary tumors only) or Cohort C where patients are randomized to co-formulated pembrolizumab + vibostolimab versus co-formulated pembrolizumab + favezelimab. The primary endpoints are complete response, disease free survival, and adverse events. Secondary endpoints include duration of response, progression free survival, disease free survival, and overall survival. The trial design for KEYNOTE-057 is as follows:
The next set of trials discussed was in the muscle invasive bladder cancer disease space, with the following summary of trials:
The first trial discussed by the panel for muscle invasive disease was the INTACT (S/N1806) trial, which is a phase 3 trial randomizing patients to radiotherapy 3D CRT or IMRT daily for 7-8 weeks + physician choice of chemotherapy versus 3D CRT –r IMRT daily for 7-8 weeks + physician choice of chemotherapy + atezolizumab for up to 9 cycles. The primary endpoint is bladder-intact event free survival, and secondary endpoints include overall survival, biopsy response, progression free survival, MFS, CSS, and quality of life. This trial is currently accruing at UC San Diego with the following trial design:
The second trial discussed was the VOLGA trial assessing the effect of neoadjuvant combination therapies. Patients will be randomized 1:1:1 to durvalumab + tremelimumab + enfortumab vedotin for 3 cycles followed by 1 cycle of post-operative tremelimumab + 9 cycles of durvalumab versus durvalumab + enfortumab vedotin for 3 cycles followed by radical cystectomy followed by 9 cycles of durvalumab versus radical cystectomy with or without approved adjuvant therapies. The primary outcome is pathologic complete response, event free survival, safety, and adverse events. Secondary outcomes include pathologic complete response, overall survival, event free survival, DSS, quality of life, and MFS. The trial design (accruing at UCLA and UC Irvine) for VOLGA is as follows:
The third trial in this disease space discussed by the panel was the HCRN GU20-444 phase 2 trial. Patients with muscle invasive disease will receive pembrolizumab and those that have a complete response will receive maintenance pembrolizumab. Those without a complete response will have either a cystectomy or chemoradiation. The primary endpoint is complete response rate, and secondary endpoints include RFS, adverse events, PDL1 expression clinical response, and tumor mutation burden clinical response. The trial design for HCRN GU20-444, accruing at City of Hope, is as follows:
The final trial in this disease space is accruing at UC Irvine and assessing adjuvant sacituzumab govitecan + nivolumab in ctDNA positive patients with muscle invasive disease (either bladder or upper tract) at high risk of recurrence. The primary endpoint for this trial is ctDNA clearance at 6 months, and secondary endpoints include adverse events, DFS, DMFS, and overall survival. The trial design is highlighted below:
In the metastatic first line setting, the one trial discussed was the KEYNOTE-D74 phase 3 trial randomizing patients 1:1 to disitamab vedotin + pembrolizumab versus standard of care chemotherapy. This trial is accruing at UCLA with a primary endpoint of progression free survival and overall survival. Secondary endpoints include objective response rate, duration of response, disease control rate, adverse events, and quality of life. The trial design for KEYNOTE-D74 is as follows:
There are several urothelial carcinoma trials in the metastatic salvage setting open in Southern California as highlighted in the following table:
The first trial discussed was the phase 3 SWOG S1937 trial accruing patients at USC. Patients in this trial will be randomized 1:1:1 to standard of care (sacituzumab govitecan or docetaxel or gemcitabine) versus eribulin (mechanism of action: inhibits microtubule growth) versus gemcitabine + eribulin. The primary endpoint for this trial is overall survival and secondary endpoints include progression free survival, complete response, objective response rate, duration of response, and disease control rate:
The second trial is a phase 2 trial accruing at UC San Diego whereby patients with cancer-associated DNA repair gene mutations will be treated with olaparib. The primary endpoint is objective response rate, and secondary endpoints include progression free survival, adverse events, and assessment by individual DNA repair defects:
The third trial in the salvage metastatic setting discussed by the panel was the KEYMAKER-U04 phase 1/2 trial from UC San Diego where patients will receive zilovertamab vedotin (mechanism of action: a cleavable, antibody drug conjugate targeting ROR1). The primary endpoint is adverse events and objective response rates, and the secondary endpoint is duration of response:
The fourth trial discussed by the panel was KEYNOTE-D78, a phase 2, multi-cohort trial enrolling at UC Irvine with several treatment options based on prior therapy received. The primary endpoints are clinical objective response rate, complete response, and adverse events. The secondary endpoints are duration of response, progression free survival, disease control rate, and overall survival. The trial design for KEYNOTE-D78 is as follows:
The fifth trial in the salvage metastatic setting was the ACR-368-201 (GOG 3082) phase 1/2 basket trial (including ovarian, urothelial, and endometrial cancer) enrolling at UC Irvine. Patients in this trial will receive ACR-368 (cell cycle checkpoint inhibitor) or ACR-368 with an ultralow dose of gemcitabine. The primary endpoints are objective response rate and adverse events, while the secondary endpoints are overall survival, duration of response, pharmacokinetics, and progression free survival:
The sixth trial discussed was the KEYNOTE-F35 phase 1a/1b from the City of Hope assessing LOXO-435 (mechanism of action: selective FGFR3 inhibitor) among patients with alterations in FGFR3. The endpoints are pharmacokinetics, duration of response, time to response, progression free survival, disease control rate, overall survival, and FACT-BI. Secondary endpoints include:
The final trial in the metastatic salvage setting discussed by the panel was the DEKA-1 phase 1 trial from the City of Hope. This trial is assessing DEKA-210 (mechanism of action: IL-10 and IL-2 couples onto a single chain variable) at different doses. The primary endpoints are adverse events and maximally tolerated dose, and secondary endpoints include objective response rate, progression free survival, overall survival, and pharmacokinetics:
Moderated by: Sia Daneshmand, MD, University of Southern California, Los Angeles, CA
Presented by:
- Abhishek Tripathi, MD, City of Hope, Duarte, CA
- Alexandra Drakaki, MD, University of California Los Angeles, Los Angeles, CA
- Aditya Bagrodia, MD, FACS, University of California San Diego, San Diego, CA
- Nataliya Mar, MD, University of California Irvine, Irvine, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 Southern California Genitourinary Cancer Research Forum, Costa Mesa, CA, Fri, Mar 1, 2024.