Sasanlimab As Maintenance Treatment Based on Clinical Response to Neoadjuvant Treatment in Molecularly Categorized Muscle Invasive Bladder Cancer Patients

NCT06623162 | Not Yet Recruiting Phase 2

• 2 other identifiers: HM-87884561EU CT
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Selective Bladder-Sparing Trial with Sasanlimab as Maintenance Treatment Based On Clinical Response To Neoadjuvant Treatment In Molecularly Categorized Muscle Invasive Bladder Cancer Patients

Conditions

Mibc; Muscle Invasive Bladder Cancer

Keywords

MIBC; sparing; cystectomy; muscle invasive bladder cancer; gemcitabine; cisplatine

Outcome Measures

Primary Outcomes (1)

• To evaluate the bladder-intact overall survival at 12 months after the first dose of sasanlimab. Bladder-intact overall survival is defined as the time from initiation of sasanlimab treatment until death or cystectomy

  The primary endpoint will be the bladder-intact overall survival rate at 12 months after the first dose of sasanlimab. Bladder-intact overall survival is defined as the time from initiation of sasanlimab treatment until death or cystectomy. The primary endpoint will be the percentage of patients who are alive and with no cystectomy at 12 months after the first dose of sasanlimab.

  12 months

Study Arms (1)

Neoadjuvant

EXPERIMENTAL

4 cycles of gemcitabine plus cisplatin

Drug: gemcitabine + cisplatine

Interventions

gemcitabine + cisplatine DRUG

4 cycles

Neoadjuvant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who sign a written informed consent approved by an IEC for the participation in this trial.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of ≤ 1 within 28 days prior to registration (Appendix 6).
• Histological evidence of localized muscle-invasive urothelial cancer of the bladder (i.e., pT2-T4 / N0 / M0). Candidate for cystectomy as per treating physician.
• Absence of metastasis as confirmed by CT or MRI scan of pelvis, abdomen and chest no more than 4 weeks pre-enrolenrment.
• Patients candidates to receive neoadjuvant therapy with gemcitabine and cisplatin. Note:MVAC treatment will not be allowed.
• All subjects must have adequate archival tissue identified at screening (i.e., at least 15 unstained slides or paraffin block). Subjects without archival tissue must be discussed with the Sponsor-investigator.
• Adequate organ and bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L.
• Hemoglobin (HgB) ≥ 9 g/dL.
• Platelet count ≥ 100 x 10\^9/L.
• Creatinine ≤ 1.5 or creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula).
• Bilirubin ≤ 1.5 × upper limit of normal (ULN). Note: subjects with Gilbert Syndrome, who have total bilirubin \< 3.0 mg/dL are eligible.
• Hepatic enzymes Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \< 3 x ULN.
• Female patients must either:

You may not qualify if:

• \. Prior treatment with systemic chemotherapy or other approved anticancer treatments for muscle-invasive urothelial cancer of the bladder. Note: In case of prior non muscle-invasive bladder cancer NMIBC, Mitomycin or Bacillus Calmette Guerin (BCG) treatment are allowed.
• \. Another malignancy that is progressing or required active treatment , with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ).
• \. Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Note: Patients with diabetes type I, vitiligo, psoriasis, or hypothyroid or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• \. Patients that have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 28 days prior to the first dose of trial treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid).
• \. History of allogeneic organ transplant. 6. Active non-infectious pneumonitis, pulmonary fibrosis, or known history of immune mediated pneumonitis.
• \. Active infection requiring systemic therapy. Patients with active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, or known HIV infection.
• \. Live attenuated vaccines within 4 weeks prior to the first dose of sasanlimab and through 30 days following the last dose of sasanlimab are not allowed.
• Note: influenza and SARS-CoV-2 vaccines which are inactivated are allowed. 9. Clinically significant cardiovascular diseases, including any of the following:
• History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft, coronary angioplasty or stenting) ≤6 months prior to start of study treatment.
• Congestive heart failure requiring treatment (New York Heart Association Class ≥2).
• Uncontrolled hypertension, defined as persistent systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg despite optimal therapy.
• History or presence of clinically significant or uncontrolled sustained cardiac arrhythmias (including uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia).
• History of thromboembolic or cerebrovascular events ≤3 months prior to the first dose of study treatment, including ischemic attacks, cerebrovascular accidents, hemodynamically significant (ie, massive or sub-massive) deep vein thrombosis or pulmonary emboli. Note: Participants with either deep vein thrombosis or pulmonary emboli that do not result in hemodynamic instability are allowed to enroll as long as they are stable, asymptomatic and on stable anticoagulants for at least 2 weeks. Note: Participants with thromboembolic events related to indwelling catheters or other procedures may be enrolled. 10. Major surgery less than 28 days prior to the first dose of study treatment. 11. Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A \[IgA\] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis.
• \. Known or suspected hypersensitivity to active ingredients or excipients of the study drug.
• \. Pregnant or breastfeeding. 14. Any serious or uncontrolled medical disorder, psychiatric or social condition that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.

Sponsors & Collaborators

• Fundación de investigación HM: lead
• MFAR Clinical Research S.L.: collaborator
• Hospital Universitario 12 de Octubre: collaborator

Study Sites (1)

Hm Sanchinarro

Madrid, Madrid, 28050, Spain

Location

Related Publications (9)

• Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013 Feb;63(2):234-41. doi: 10.1016/j.eururo.2012.07.033. Epub 2012 Jul 25.

  PMID: 22877502 BACKGROUND

• Bruck K, Meijer RP, Boormans JL, Kiemeney LA, Witjes JA, van Hoogstraten LMC, van der Heijden MS, Donders AR, Franckena M, Uyl de Groot CA, Leliveld AM, Aben KKH, Hulshof MCCM. Disease-Free Survival of Patients With Muscle-Invasive Bladder Cancer Treated With Radical Cystectomy Versus Bladder-Preserving Therapy: A Nationwide Study. Int J Radiat Oncol Biol Phys. 2024 Jan 1;118(1):41-49. doi: 10.1016/j.ijrobp.2023.07.027. Epub 2023 Jul 28.

  PMID: 37517601 BACKGROUND

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 BACKGROUND

• Brahmer JR, Abu-Sbeih H, Ascierto PA, Brufsky J, Cappelli LC, Cortazar FB, Gerber DE, Hamad L, Hansen E, Johnson DB, Lacouture ME, Masters GA, Naidoo J, Nanni M, Perales MA, Puzanov I, Santomasso BD, Shanbhag SP, Sharma R, Skondra D, Sosman JA, Turner M, Ernstoff MS. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2021 Jun;9(6):e002435. doi: 10.1136/jitc-2021-002435.

  PMID: 34172516 BACKGROUND

• Bellmunt J, Hussain M, Gschwend JE, Albers P, Oudard S, Castellano D, Daneshmand S, Nishiyama H, Majchrowicz M, Degaonkar V, Shi Y, Mariathasan S, Grivas P, Drakaki A, O'Donnell PH, Rosenberg JE, Geynisman DM, Petrylak DP, Hoffman-Censits J, Bedke J, Kalebasty AR, Zakharia Y, van der Heijden MS, Sternberg CN, Davarpanah NN, Powles T; IMvigor010 Study Group. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):525-537. doi: 10.1016/S1470-2045(21)00004-8. Epub 2021 Mar 12.

  PMID: 33721560 BACKGROUND

• Balar et al. 2021 Balar AV, Milowsky MI, O'Donnell PH, et al. Pembrolizumab (pembro) in combination with gemcitabine (Gem) and concurrent hypofractionated radiation therapy (RT) as bladder sparing treatment for muscle-invasive urothelial cancer of the bladder (MIBC): A multicenter phase 2 trial. J. Clin. Oncol. 2021;39:4504.

  BACKGROUND

• Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Ye D, Agerbaek M, Enting D, McDermott R, Gajate P, Peer A, Milowsky MI, Nosov A, Neif Antonio J Jr, Tupikowski K, Toms L, Fischer BS, Qureshi A, Collette S, Unsal-Kacmaz K, Broughton E, Zardavas D, Koon HB, Galsky MD. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021 Jun 3;384(22):2102-2114. doi: 10.1056/NEJMoa2034442.

  PMID: 34077643 BACKGROUND

• Al-Khami AA, Youssef S, Abdiche Y, Nguyen H, Chou J, Kimberlin CR, Chin SM, Kamperschroer C, Jessen B, Kern B, Budimir N, Dillon CP, Xu A, Clark JD, Chou J, Kraynov E, Rajpal A, Lin JC, Salek-Ardakani S. Pharmacologic Properties and Preclinical Activity of Sasanlimab, A High-affinity Engineered Anti-Human PD-1 Antibody. Mol Cancer Ther. 2020 Oct;19(10):2105-2116. doi: 10.1158/1535-7163.MCT-20-0093. Epub 2020 Aug 26.

  PMID: 32847983 BACKGROUND

• Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol. 2005 Aug;48(2):202-5; discussion 205-6. doi: 10.1016/j.eururo.2005.04.006. Epub 2005 Apr 21.

  PMID: 15939524 BACKGROUND

MeSH Terms

Interventions

Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Elena Sevillano Fernandez, PhD

CONTACT

+34917567984; esevillano@hmhospitales.com

Guillermo de Velasco Oria de Rueda, MD, PhD

CONTACT

+34 91 390 83 39; gdevelasco.gdv@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 2, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 4, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)