https://orcid.org/0000-0002-8841-8676
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Abstract
The utilization of neoadjuvant immune checkpoint inhibitor therapy, specifically anti-PD-1/L1 agents, prior to radical cystectomy is an emerging paradigm in muscle-invasive bladder cancer (MIBC). In situ vaccination represents a strategy to manipulate the tumor in order to augment the immune response toward improved local and distant cancer control. The authors describe the study rationale, design and objectives for RAD VACCINE MIBC, a single-arm, single-institution, phase II trial evaluating the efficacy and safety of combination neoadjuvant sasanlimab (humanized IgG monoclonal antibody that targets PD-1) with stereotactic body radiotherapy as an in situ vaccine in cisplatin-ineligible patients with MIBC. The results from this trial will establish the safety profile of this combination strategy and evaluate pathologic complete response rates.
Plain language summary
RAD VACCINE MIBC is a phase II clinical trial that aims to determine the safety and effectiveness of a study drug called sasanlimab (an immune checkpoint inhibitor), combined with radiation therapy (stereotactic body radiation therapy) prior to surgery to remove the bladder (known as radical cystectomy [RC]) in muscle-invasive bladder cancer patients. For this type of cancer, patients typically receive chemotherapy followed by RC as the standard of care. However, many patients who have pre-existing medical conditions such as poor kidney function are unable to receive chemotherapy. These patients undergo RC alone at the risk of less optimal cancer control. Bladder cancer is known to inhibit the immune cells (T cells) from attacking it, which is an important way in which the body controls cancer cells. Sasanlimab allows T cells that are specific to the cancer to potentially reactivate. Ongoing studies have shown that drugs similar to sasanlimab can be used to achieve improvement in cancer control in the bladder (as measured by shrinking the cancer or eradicating it) before surgery. The authors are studying the use of the study drug with the addition of stereotactic body radiotherapy (SBRT) as a combined therapy. The role of SBRT as a combined therapy to immune checkpoint inhibition has been well studied to help improve the process of how immune cells recognize cancer cells. By giving both the study drug and SBRT together before RC, the authors aim to demonstrate the safety of this technique and its effectiveness in eradicating all cancer in the bladder.
Clinical Trial Registration: NCT05241340 (ClinicalTrials.gov)
Tweetable abstract
A phase II trial evaluating a novel strategy of combination neoadjuvant immune checkpoint inhibition with sasanlimab and stereotactic body radiotherapy as an in situ vaccine in cisplatin-ineligible patients with muscle-invasive #BladderCancer
Financial & competing interests disclosure
Investigator sponsored research grant for drug (sasanlimab), Pfizer, Inc. Clinician Trialist Award, Houston Methodist Academic Institute, Houston Methodist Hospital R Satkunasivam: consultant for Intuitive Surgical, Inc.; research funding from Pfizer, Bristol-Myers Squibb, Anchiano, QED Therapeutics, Merck, CoImmune, Natera. J Zhang: honoraria and consulting/advisory role for Genentech. SH Chen: consulting/advisory role for Ansun Biopharma; patents/royalties/other intellectual property from Ansun Biopharma for self and an immediate family member. C Wallis: consulting fees from Janssen Oncology, SESEN Bio, Precision Point Specialty LLC; honoraria from EMD Serono, Haymarket Media, Healing and Cancer Foundation, Knight Therapeutics, Tolmar Pharmaceuticals Canada. E Efstathiou: consulting/advisory role for Sanofi, Janssen Oncology, Tokai Pharmaceuticals, AstraZeneca, Myovant Sciences, Bayer; honoraria for Sanofi, Janssen-Cilag, Astella Pharma, Takeda, Merck, Pfizer; research funding from Janssen-Cilag. NF Esnaola: consulting/advisory role for AngioDyanmics. GP Sonpavde: consulting/advisory role for Genetech, Merck, Eisai, AstraZeneca, Janssen, Bristol Myers Squibb, Exelixis, EMD Serono, Astella Pharma, Bicycle Therapeutics, Pfizer, Seattle Genetics, Gilead Sciences, Scholar Rock, G1 Therapeutics, Loxo/Lilly, Infinity Pharmaceuticals; speakers’ bureau for Physicians’ Education Resource, OncLive, Research to Practice, Medscape; travel, accommodations, expenses from Bristol Myers Squibb; honoraria for UpToDate; research funding for author’s institution from Janssen, Sanofi, AstraZeneca, Gilead Sciences, QED Therapeutics, Bristol Myers Squibb, Predicine, EMD Serono; has an immediate family member employed for Myriad Genetics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.