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Clinical research

An Ongoing Phase II Clinical Trial for Bladder Cancer

Combining Neoadjuvant Drug Sasanlimab and Stereotactic Body Radiotherapy May Improve The Quality Of Life In Muscle-Invasive Bladder Cancer Patients

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Houston Methodist is leading an ongoing Phase II clinical trial that is designed to evaluate the safety and efficacy of combining Pfizer’s neoadjuvant drug sasanlimab, a humanized IgG monoclonal antibody that selectively targets programmed cell death protein-1, with stereotactic body radiotherapy (SBRT) in patients suffering from muscle-invasive bladder cancer (MIBC). The results of this trial, led by Raj Satkunasivam, MD, Associate Professor of Urology, may pave the way for developing novel therapies for bladder cancer treatment. The American Cancer Society estimates there will be about 81,000 new cases of bladder cancer in 2022, which will result in about 17,000 deaths. For approximately one in four bladder cancer cases, the cancer has spread into the detrusor muscle of the bladder. This situation requires more extensive surgical and treatment interventions.
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Raj Satkunasivam, MD
The typical treatment for MIBC is chemotherapy followed by a radical cystectomy (RC) that typically includes removal of reproductive structures in addition to the entire bladder. However, in many cases, patients undergo RC without chemotherapy since their pre-existing medical conditions preclude chemotherapy treatment. This category of patients is subject to sub-optimal cancer control and the risks thereof. Bladder cancer prevents T cells from attacking cancer cells, which diminishes cancer control. As an immune checkpoint inhibitor, sasanlimab revives bladder cancer-specific T cells to attack cancerous cells and is used to shrink or eliminate the tumor. It may also prevent the tumor cells from growing or spreading. SBRT is aimed at augmenting the recognition of cancer cells by immune cells. In this trial, a combination of sasanlimab and SBRT is being evaluated for safety and efficacy in eliminating all cancer cells in the bladder. The trial is a single-institution, prospective single-arm trial to test this combination strategy in MIBC patients that are cisplatin-ineligible or refusing cisplatin-based chemotherapy before radical cystectomy (RC). Cisplatin is a potent first-line chemotherapy treatment for various malignancies including MIBC. Satkunasivam published the details of the clinical trial protocol in Future Oncology in 2022.
Patients diagnosed with MIBC have a poor prognosis, especially if they are ineligible to receive neoadjuvant cisplatin-based chemotherapy. The current standard of care in this population is radical cystectomy alone followed by systemic therapy at the time of disease relapse. Therefore, there is a clinically significant unmet need for novel neoadjuvant approaches in this population. RAD VACCINE MIBC will assess the safety and efficacy of neoadjuvant sasanlimab combined with SBRT as an in-situ vaccine in cisplatin-ineligible patients with MIBC. This study builds upon the promising role of radiation as an immune-stimulatory mechanism in the context of immune checkpoint inhibition. This combination therapy has the potential to be well tolerated and to improve loco-regional control for this patient population.”
Raj Satkunasivam, MD
Satkunasivam based this clinical trial on the hypothesis that the combination strategy is safe, feasible and enhances the pathologic complete response rates relative to cisplatin-based chemotherapy or immune checkpoint inhibitor monotherapy. The 33 patients enrolled in this trial at Houston Methodist receive sasanlimab administration daily for a cycle of 28 days followed by the combination therapy for another 28 days. The primary endpoints were safety and feasibility of the combination therapy whereas the secondary endpoints included adverse events, surgical complication rates, quality of life, overall survival and recurrence-free survival. “Patients diagnosed with MIBC have a poor prognosis, especially if they are ineligible to receive neoadjuvant cisplatin-based chemotherapy,” said Satkunasivam. “The current standard of care in this population is radical cystectomy alone followed by systemic therapy at the time of disease relapse. Therefore, there is a clinically significant unmet need for novel neoadjuvant approaches in this population. RAD VACCINE MIBC will assess the safety and efficacy of neoadjuvant sasanlimab combined with SBRT as an in-situ vaccine in cisplatin-ineligible patients with MIBC. This study builds upon the promising role of radiation as an immune-stimulatory mechanism in the context of immune checkpoint inhibition. This combination therapy has the potential to be well tolerated and to improve loco-regional control for this patient population.”
Raj Satkunasivam, Kelvin Lim, Bin S Teh, Jonathan Guzman, Jun Zhang, Andrew Farach, Shu-Hsia Chen, Christopher Jd Wallis, Eleni Efstathiou, Nestor F Esnaola, Guru P Sonpavde. A phase II clinical trial of neoadjuvant sasanlimab and stereotactic body radiation therapy as an in situ vaccine for cisplatin-ineligible MIBC: the RAD VACCINE MIBC trial. Future Oncol. 2022 Aug;18(25):2771-2781.
Abanti Chattopadhyay, PhD
March 2023
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