Sasanlimab Treatment As Bladder-Sparing Strategy For Patients With Muscle Invasive Bladder Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion De investigacion De Hm Hospitales

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Nov 2024 → ongoing

Decision date (initial)

2024-07-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Fundación de Investigación HM Hospitales · Pfizer

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

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

Secondary objectives 6

1. Secondary Efficacy Objectives ● To evaluate the disease-free survival (DFS) defined as the time from the first dose of sasanlimab to the first occurrence of a DFS event, defined as any of the following: ○ Local (pelvic) recurrence of urothelial carcinoma (UC) (including soft tissue and regional lymph nodes) ○ Urinary tract recurrence of UC ○ Distant metastasis of UC ○ Death from any cause
2. Secondary Efficacy Objectives: ●To evaluate the metastasis free survival (MFS) defined as the time from the first dose of sasanlimab to the first occurrence of distant metastasis of UC or death from any cause.
3. Secondary Efficacy Objectives: ●To evaluate the overall survival (OS) defined as the time from the first dose of sasanlimab to death.
4. Secondary Efficacy Objectives: ●To evaluate the clinical response rate (cT0 or cTa or cT1/Tis) at 12 months with neoadjuvant gemcitabine, cisplatin.
5. Secondary Efficacy Objectives: ●To evaluate the quality of life of patients who undergo bladder-sparing therapy with sasanlimab maintenance.
6. Secondary Safety Objectives ● To evaluate the safety of sasanlimab maintenance after neoadjuvant gemcitabine, cisplatin.

Conditions and MedDRA coding

Molecularly Categorized Muscle Invasive Bladder Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Patients who sign a written informed consent approved by an IEC for the participation in this trial.
2. Age ≥ 18 years at the time of consent.
3. ECOG Performance Status of ≤ 1 within 28 days prior to registration (Appendix 6).
4. Histological evidence of localized muscle-invasive urothelial cancer of the bladder (i.e., pT2-T4 / N0 / M0). Histological variants are allowed if the urothelial component is predominantly. Candidate for cystectomy as per treating physician.
5. Absence of metastasis as confirmed by CT or MRI scan of pelvis, abdomen and chest no more than 4 weeks pre-enrolment.
6. Patients candidates to receive neoadjuvant therapy with gemcitabine and cisplatin. Note:MVAC treatment will not be allowed.
7. 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.
8. Adequate organ and bone marrow function as defined below: a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. b. Hemoglobin (HgB) ≥ 9 g/dL. c. Platelet count ≥ 100 x 109/L. d. Creatinine ≤ 1.5 or creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula). e. Bilirubin ≤ 1.5 × upper limit of normal (ULN). Note: subjects with Gilbert Syndrome, who have total bilirubin < 3.0 mg/dL are eligible. f. Hepatic enzymes Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 3 x ULN.
9. Female patients must either: a. Be of nonchildbearing potential: i. Postmenopausal *(defined as at least 1 year without any menses) prior to screening , or ii. Documented surgically sterile (e.g. hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or bilateral tubal occlusion). *Those who are amenorrheic due to an alternative medical cause are not considered postmenopausal and must follow the criteria for childbearing potential subjects. OR b. If of childbearing potential: i. Agree not to try to become pregnant during the study and for at least 6 months after the final study drug administration, ii. And have a negative urine or serum pregnancy test within 7 days prior to Day 1 (females with false positive results and documented verification of negative pregnancy status are eligible for participation), iii. And if heterosexually active, agree to abstinence (if in line with the usual preferred lifestyle of the patient) or consistently use a condom plus 1 form of highly effective birth control (Appendix 7) per locally accepted standards starting at screening and throughout the study period and for a
10. Female patients must agree not to breastfeed or donate ovules starting at screening and throughout the study period, and for at least 6 months after the final study drug administration.
11. Male patients with a partner with childbearing potential, or who is pregnant or breastfeeding must agree to abstinence or use a condom plus 1 form of highly effective birth control throughout the study period and for at least 6 months after the final study drug administration.
12. Male patients must not donate sperm starting at screening and throughout the study period, and for at least 6 months after the final study drug administration.
13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
14. Patient agrees not to participate in another interventional study while on treatment in the present study.

Exclusion criteria 14

1. 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.
2. 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).
3. 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.
4. 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).
5. History of allogeneic organ transplant.
6. Active non-infectious pneumonitis, pulmonary fibrosis, or known history of immune- mediated pneumonitis.
7. Active infection requiring systemic therapy. Patients with active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, or known HIV infection.
8. 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: a. 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. b. Congestive heart failure requiring treatment (New York Heart Association Class ≥2). c. Uncontrolled hypertension, defined as persistent systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg despite optimal therapy. d. History or presence of clinically significant or uncontrolled sustained cardiac arrhythmias (including uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia). e. 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.
12. Known or suspected hypersensitivity to active ingredients or excipients of the study drug.
13. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 3

1. Secondary Efficacy Endpoints ● Clinical response rate, defined as absence of muscle-invasive cancer after cisplatin-based treatment (≤cT1). ● Disease-free survival (DFS) according to Section 8.1. ● Metastasis-free survival (MFS) according to RECIST v1.1 (Appendix 3). ●Overall survival (OS). ● Health-related quality of life (HRQoL), assessed through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) version 3 (Appendix 4).
2. Secondary Safety Endpoints ●Frequency and severity of adverse events and treatment-related adverse events (TRAEs) assessed by NCI CTCAE v5.0 (Appendix 5). ● Frequency of AEs leading to treatment discontinuation.
3. Secondary Exploratory Endpoints: ● Correlation of baseline ctDNA levels with efficacy endpoints. ● Correlation between tumor markers from TURBT biopsy at baseline and benefit of maintenance treatment with sasanlimab. ●Changes in ctDNA levels in blood samples throughout the study treatment period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion De investigacion De Hm Hospitales

Sponsor organisation

Fundacion De investigacion De Hm Hospitales

Address

Plaza Del Conde Del Valle De Suchil 2

City

Madrid

Postcode

28015

Country

Spain

Scientific contact point

Organisation

Fundacion De investigacion De Hm Hospitales

Contact name

A person designed by the Sponsor

Public contact point

Organisation

Fundacion De investigacion De Hm Hospitales

Contact name

A person designed by the Sponsor

Third parties 2

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications