KEY TAKEAWAYS
- The Phase 2 KEYNOTE-057 trial will evaluate the effectiveness and safety of coformulations of pembro with either TIGIT inhibitor vibostolimab.
- Approximately 60 patients will be randomly allocated to Arm 1 or Arm 2 and receive intravenous treatment every three weeks for a maximum of 35 administrations.
- The primary outcome is the 12-month complete response rate of high-risk NMIBC, as evaluated by central pathology.
- Patients must have been diagnosed with high-risk non-muscle invasive bladder cancer that has not responded to Bacillus Calmette-Guérin therapy.
- Pembrolizumab has been authorized in the United States to manage patients diagnosed with high-risk non-muscle invasive bladder cancer.
The PD-1 inhibitor pembro demonstrated antitumor activity in cohort A of the phase 2 KEYNOTE-057 study (NCT02625961). Approximately 41% of patients diagnosed with HR BCG-unresponsive carcinoma in situ (CIS) of the bladder ± papillary tumors achieved a complete response (CR) at 3 months, with a median duration of response (DOR) of 16.2 months. According to these findings, Pembrolizumab has been authorized in the United States to manage patients diagnosed with high-risk non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG) therapy is accompanied by carcinoma in situ and/or papillary tumors. This treatment option is recommended for patients who are not suitable candidates for or have declined radical cystectomy. Novel combinations that enhance the efficacy of pembrolizumab are required. The inhibition of immune checkpoints TIGIT and LAG-3 has been demonstrated to play a role in developing treatment resistance in various malignancies. Consequently, their suppression may potentially augment the efficacy of pembro. The efficacy and safety of coformulations of pembro and TIGIT inhibitor vibostolimab or LAG-3 inhibitor favezelimab will be evaluated in patients with high-risk Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer with carcinoma in situ and papillary tumors in Cohort C of the KEYNOTE-057 trial.
The primary requirements for participation in this study are adults diagnosed with histologically confirmed high-risk non-muscle invasive bladder cancer that has not responded to Bacillus Calmette-Guérin therapy. This is defined as the presence of persistent or recurrent carcinoma in situ alone or with papillary tumors of Ta/T1 stage within 12 months of completion of adequate Bacillus Calmette-Guérin therapy. Additionally, these individuals must be ineligible for or have chosen not to undergo radical cystectomy, have CIS ± papillary tumors at baseline (CIS alone, Ta + CIS or T1 + CIS), and have an Eastern Cooperative Oncology Group performance status score of 0-2. Approximately 60 patients will be randomly allocated in a 1:1 ratio to Arm 1, which involves the co-formulation of pembro 200 mg and vibostolimab 200 mg, or Arm 2, which involves the co-formulation of pembro 200 mg and favezelimab 800 mg. The administration will be intravenous every three weeks for a maximum of 35 administrations until central pathology confirms ≥T1 at any time point or persistent or recurrent CIS or high-grade ≥Ta at the 24-week efficacy review or later. Patients diagnosed with centrally located pathology-confirmed low-grade pTa at any given time may proceed with treatment after removing visible tumors. In the event of the non-existence of disease persistence/recurrence or progression, the treatment shall persist until intolerable toxicity, determination to discontinue, or administrative grounds. Tumour assessments shall be conducted every 12 weeks until the second year and then every 24 weeks after that for a maximum of 5 years. The principal effectiveness endpoint is the 12-month complete response rate of high-risk non-muscle invasive bladder cancer, evaluated by central pathology and radiology review through cystoscopy, cytology, biopsy, and radiologic imaging. The secondary efficacy endpoints comprise the duration of response (DOR) of high-risk non-muscle invasive bladder cancer (HR NMIBC) in responders, complete response (CR) rate overall and at 3 and 6 months, progression-free survival (PFS) to worsening of grade, stage, or death, PFS to muscle-invasive or metastatic disease or death, and overall survival (OS). The safety objective aims to assess the safety and tolerability of the study treatment in all patients who have received at least one dose. The effectiveness assessment will be conducted on all patients who have been administered at least one dose of the study medication and have undergone a pre-enrollment cystoscopy, TURBT/biopsy, urine cytology, and baseline CT urography imaging.
Source:https://meetings.asco.org/abstracts-presentations/216866
Clinical Trail:https://clinicaltrials.gov/ct2/show/NCT02625961
Neal D. Shore, Shilpa Gupta, Girish S. Kulkarni, Andrea Necchi, Hema Kishore Dave, Ekta Kapadia, Qing Zhao, Ashish M. Kamat/Phase 2 KEYNOTE-057 cohort C: Pembrolizumab (pembro) with vibostolimab or favezelimab for patients (pts) with high-risk (HR) bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC)/J Clin Oncol 41, 2023 (suppl 6; abstr TPS591) DOI10.1200/JCO.2023.41.6_suppl.TPS591
