Bladder CancerPhase 2preSAVENCT06528483
Bladder Preservation With Sacituzumab Govitecan + Zimberelimab for Muscle-Invasive Bladder Cancer
A Phase 2 study testing Sacituzumab Govitecan + Zimberelimab in people with Bladder Cancer and Bladder Urothelial Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
Patients with MIBC N0/N1 unwilling or unfit for cystectomy will receive SG + Zimberelimab for 3 cycles of treatment prior of first radiological and TURB re-evaluation. Patients with stable disease or downstaging will continue Zimberelimab up to 1 year. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Bladder Urothelial Carcinoma, Bladder Neoplasm
- What is being tested?
- Sacituzumab Govitecan + Zimberelimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteItaly
- Study dates
- 2 Dec 2024to 31 Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant is at least 18 years old of age, at the time of providing informed consent.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
- Patients deemed ineligible for Radical Cystectomy (RC) + Retroperitoneal lymphnode dissection (RPNLD) by a urologist and/or oncologist and/or anesthesiology.
- Cisplatin unfit patients as per Galsky criteria (ECOG Performance Status of 2 and/or creatinine-clearance < 60 ml/min and/or CTCAE Gr ≥ 2 hearing loss and/or CTCAE Gr ≥ 2 neuropathy).
- Cisplatin-fit patients are admitted if they are unwilling to undergo Radical Cystectomy (RC) and unwilling for cisplatin-based chemotherapy.
Show all 20Show fewer
- Patients deemed eligible for surgery will be included if they will be unwilling to undergo RC and will be ineligible and/or unwilling to cisplatin-based chemotherapy.
- cT2-cT4 bladder cancer patients with predominant urothelial histology or Squamous cell histologic variant with histological confirmed diagnosis of muscle-invasive bladder cancer (MIBC) obtained via a diagnostic or maximal TURBT performed within 90 days before enrollment.
- cN0-1 bladder cancer patients with predominant urothelial histology or Squamous cell histologic variant
- Have adequate organ function as defined as follow (Specimens must be collected within 10 days prior to the start of study intervention):
- Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study treatment initiations (hemoglobin ≥ 9 g/dL, ANC ≥ 1500/mm3, and platelets ≥ 100,000/μL).
- Adequate hepatic function (bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5 × ULN or ≤ 5 × ULN if known liver metastases, and serum albumin > 3 g/dL).
- Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation.
- International normalized ratio (INR)/PT and PTT or aPTT ≤ 1.5 ULN unless patient is currently receiving therapeutic anticoagulant therapy.
- Patients with HIV must be on antiretroviral therapy (ART) and have a well-controlled
- HIV infection/disease defined as:
- Patients on ART must have a CD4+ T-cell count ≥ 350 cells/mm3 at time of screening.
- Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening.
- Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1).
- The combination ART regimen must not contain any medications that may interfere with SN-38 metabolism.
Who cannot join
- Positive serum pregnancy test (Appendices 9.4) or women who are breastfeeding.
- Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
- Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section.
- Have had a prior anticancer biologic agent within 4 weeks prior to enrollment or have had prior chemotherapy or targeted small molecule therapy. Patients participating in observational studies are eligible.
- Have previously received topoisomerase 1 inhibitors.
- Have an active second malignancy. Note: patients with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll. Other exception are localized prostate cancer with a Gleason score of 6 (treated within the last 24 months or untreated and under surveillance) and localized prostate cancer with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence.
Show all 16Show fewer
- Patients with neuroendocrine histology will be excluded.
- Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of enrollment.
- Have active serious infection requiring antibiotics.
- Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody, if done at screening) with detectable viral load OR taking medications that may interfere with SN-38 metabolism.
- Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with a history of HBV or HCV, patients with detectable viral loads will be excluded.
- Patients who test positive for hepatitis B surface antigen (HBsAg). Patients who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease.
- Patients who test positive for HCV antibody. Patients who test positive for HCV antibody will require HCV RNA by quantitative PCR for confirmation of active disease. Patients with a known history of HCV or a positive HCV antibody test will not require a HCV antibody at screening and will only require HCV RNA by quantitative PCR for confirmation of active disease.
- Have other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
- Any medical condition that, in the investigator's or sponsor's opinion, poses an undue risk to the patient's participation in the study.
- Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drug.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
Fondazione Irccs Istituto Nazionale Dei Tumori Di Milano
Milan, 20133
About this study
Official title: Bladder Preservation With Sacituzumab Govitecan + Zimberelimab for Muscle-Invasive Bladder Cancer in Cisplatin-unfit and Unwilling for Cystectomy Patients: Phase II Trial
Patients with MIBC N0/N1 unwilling or unfit for cystectomy will receive SG + Zimberelimab for 3 cycles of treatment prior of first radiological and TURB re-evaluation.
Patients with stable disease or downstaging will continue Zimberelimab up to 1 year. The goal of this trial is to demonstate that Sacituzumab Govitecan + Zimberelimab can avoid cistectomy and can prolong or avoid recurrence to metastatic disease in selected patients with muscle-invasive bladder cancer.
The primary endpoint of this trial is Event Free Survival that is defined as clinical evidence of new or progressing nodal or any distant metastatic disease, radical cystectomy, or death due to any cause from date of inclusion to the first documentation of a EFS event.
Read the detailed description
This is an open-label, multi-center, single-group, phase 2 study. Patients with MIBC N0/N1 unwilling or unfit for cystectomy will receive SG + Zimberelimab for 3 cycles of treatment prior of first radiological and TURB re-evaluation.
Approximately 63 patients will be enrolled and assigned to study intervention. At screening, a tumor specimen from TURBT or biopsy done as early as 90 days prior to enrollment will be submitted for central pathology review. All participants will undergo baseline screening imaging (CT or MRI of the chest, abdomen, pelvis) for clinical staging.
Eligible participants will be allocated to study intervention which consist in SG + Zimberelimab for 3 cycles followed by Zimberelimab for 13 cycles in patients who achieve CR/PR/SD at tumor evaluation.
The planned total duration of treatment is approximately 1 year, 3 cycles of SG and 16 cycles of Zimberelimab.
Treatment will be discontinued if the participant experiences unacceptable AE(s), intercurrent illness that prevents further administration of treatment, the investigator's decision to withdraw the participant, the participant withdraws consent, pregnancy of the participant, noncompliance with study intervention or procedure requirements, or the maximum number of cycles has been received for each treatment component individually.
Participants will complete 3 cycles of induction study intervention, followed by repeat imaging studies (same modality as screening) within ≤4 weeks (21 days +/- 7 days) after C3D21 to exclude disease progression. mpMRI/contrast-enhanced or CT scan will assess local invasion by T3 disease or higher and the radiological response to treatment.
Participants who remain radiographically free of distant metastases and PR/SD/CR RECIST v1.1 will proceed to TURBT within 6 weeks of the last dose of SG. TURBT will enable histopathological re-staging and will evaluate pathological response to treatment. The inclusion of bladder muscle in the resection specimen is required. Cystoscopy will be performed before TURBT, as indicated in the Schedule of Activities.
Patients with no evidence of disease at the cystoscopy, will undergo bladder mapping in case of positive urine cytology. In case of negative urine cytology, patients will be considered in as complete respose, in case of no evidence of disease at radiological evaluation.
Participants with radiological progression to metastatic disease or locally advanced disease (from cT2 to cT4 or from N0 to N1), as assessed radiographically, at this time will be considered to have met the primary endpoint of EFS (ie, had an "event") and will not receive further therapy on study, but will transition into survival follow-up and will be treated as per clinical practice.
Participants with pathological downstaging and radiological complete or partial response will continue to receive zimberelimab for 13 cycles (16 cycles as a total) to complete approximately 1 year of total therapy.
Non-responder patients who will maintain radiological or pathological stability will choose to undergo RC or RT/CT or to continue Zimberelimab for 1 years. Additional TURBT could be performed in order to achieve local control, according to the centre clinical practice.
Response to study intervention will be assessed through TURBT and CT SCAN and/or MRI. Imaging should continue to be performed until an EFS event occurs or withdrawal of consent, whichever occurs first. If new anticancer therapy is initiated, this should be documented.
All subjects will be followed for OS every 3 months until death, lost to follow-up, or withdrawal of study consent. Additional survival follow-up may continue for up to 3-5 years from the time of this analysis. To evaluate metastasis free survival, subjects will be monitored by radiographic assessment and cystoscopy on an every-12-week schedule (±5 days). RECIST 1.1 criteria will be used for the assessment. Subjects will be evaluated at every SG + Zimberelimab dose administration plus two additional follow-up visits for safety within the first 100 days from the last dose of study therapy. Beyond 100 days from the last dose of study therapy, subjects will be followed for ongoing drug-related adverse events until resolved, return to baseline or deemed irreversible, or until lost to follow-up, or withdrawal of study consent.
To assess local recurrence, cystoscopy will be performed every 12 weeks (+/- 1 7 days). In case of local recurrence, patients could be managed with TURBT as per clinical practice, in case patients will still be unfit for cystectomy or refuse surgery.
- Conditions
- Bladder Cancer, Bladder Urothelial Carcinoma, Bladder Neoplasm, Muscle-Invasive Bladder Carcinoma
- Being tested
- Sacituzumab Govitecan + Zimberelimab
- Keywords
- bladder cancer, muscle-invasive bladder cancer, bladder sparing
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacituzumab Govitecan + ZimberelimabDrug
Also called TRODELVY, AB122
Sacituzumab Govitecan 7.5 mg/kg IV for 3 cycles Zimberelimab 360 mg IV for 16 cycles
Patients will be treated with Sacituzumab Govitecan 1,8q21 plus + Zimberelimab q21 for 3 cycles then radiological imaging and TURB will be repeated and patients with Stability of disease or down staging will continue Zimberelimab until disease progression, or unacceptable toxicities or completion of treatment (16 cycles). Patients with progressive disease after 3 cycles of study intervention will be treated as per clinical practice.
| Study group | Role | What they receive |
|---|---|---|
| Sacituzumab Govitecan + Zimberelimab | Experimental | patients will be treated with Sacituzumab Govitecan 1,8q21 plus + Zimberelimab q21 for 3 cycles then radiological imaging and TURB will be repeated and patients with Stability of disease or down staging will continue Zimberelimab until disease progression, or unacceptable toxicities or completion of treatment (16 cycles). Patients with progressive disease after 3 cycles of study intervention will be treated as per clinical practice. Receives: Drug: Sacituzumab Govitecan + Zimberelimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-Free Survival (EFS)
clinical evidence of new or progressing nodal or any distant metastatic disease, radical cystectomy, or death due to any cause from date of inclusion to the first documentation of a EFS event. Patients last known to be EFS event-free are censored at the date of last event-free cystoscopy and/or CT scan. Those patients without disease assessment who are still alive will be censored at date of inclusion in the trial
Measured: 24 months
Secondary outcomes (6)
clinical or pathological downstaging
Participants experiencing partial response according to RECIST v1.1 criteria and/or pathological downstaging as from pT2 to non muscle-invasive disease after SG + Zimberelimab treatment
Measured: 24 months
Number of Participants treated with Pembrolizumab + Enfortumab Vedotin who experience AEs/SAEs
The incidence of, causality, and outcome of AEs/SAEs. AEs will be assessed as defined by CTCAE, Version [5.0]
Measured: 24 months
predictive role of miRNA in patients who achieve clinical or pathological downstaging after SG + Zimberelimab treatment
miRNA expression in partecipants who achieve clinical or pathological downstaging after SG + Zimberelimab treatment
Measured: 24 months
predictive role of ctDNA in patients who achieve clinical or pathological downstaging after SG + Zimberelimab treatment
- ctDNA expression in partecipants who achieve clinical or pathological downstaging after SG + Zimberelimab treatment
Measured: 24 months
role of 18FDG-PET in the prediction of response or relapse for N positive patients
Patients experiencing nodal progression or remission after SG + ZIM treatment
Measured: 24 months
the role of multiparametric MRI (mpMRI) in the assessment of clinical response
Patients with tumor response identified by MRI
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2024
- Study start2 Dec 2024 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Giuseppe Procopio, MD, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06528483
- Sponsor's protocol ID
- PreSAVE INT 2024
- Acronym
- preSAVE
- Status last verified
- Jul 2024
- First submitted
- 19 Jul 2024
- Last updated
- 30 Jul 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bokarica P, Hrkac A, Gilja I. Re: J. Alfred Witjes, Thierry Lebret, Eva M. Comperat, et al. Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. Eur Urol 2017;71:462-75. Eur Urol. 2017 Aug;72(2):e45. doi: 10.1016/j.eururo.2017.02.031. Epub 2017 Mar 6. No abstract available.
PubMed 28279514Softness K, Kaul S, Fleishman A, Efstathiou J, Bellmunt J, Kim SP, Korets R, Chang P, Wagner A, Olumi AF, Gershman B. Radical cystectomy versus trimodality therapy for muscle-invasive urothelial carcinoma of the bladder. Urol Oncol. 2022 Jun;40(6):272.e1-272.e9. doi: 10.1016/j.urolonc.2021.12.015. Epub 2022 Jan 17.
PubMed 35058142Royce TJ, Feldman AS, Mossanen M, Yang JC, Shipley WU, Pandharipande PV, Efstathiou JA. Comparative Effectiveness of Bladder-preserving Tri-modality Therapy Versus Radical Cystectomy for Muscle-invasive Bladder Cancer. Clin Genitourin Cancer. 2019 Feb;17(1):23-31.e3. doi: 10.1016/j.clgc.2018.09.023. Epub 2018 Oct 4.
PubMed 30482661Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. doi: 10.1016/S1470-2045(13)70255-9. Epub 2013 Jul 1.
PubMed 23823157James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, Crundwell M, Sizer B, Sreenivasan T, Hendron C, Lewis R, Waters R, Huddart RA; BC2001 Investigators. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012 Apr 19;366(16):1477-88. doi: 10.1056/NEJMoa1106106.
PubMed 22512481Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18.
PubMed 32945632Powles T, Bellmunt J, Comperat E, De Santis M, Huddart R, Loriot Y, Necchi A, Valderrama BP, Ravaud A, Shariat SF, Szabados B, van der Heijden MS, Gillessen S; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Mar;33(3):244-258. doi: 10.1016/j.annonc.2021.11.012. Epub 2021 Nov 30. No abstract available.
PubMed 34861372Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
PubMed 28055103Lin N, Zhang M, Bai H, Liu H, Cui J, Ke X, Zhang H, Liu L, Yan D, Jiang Y, Zang A, Qi J, Wang L, Liu Z, Xu B, Zhang Y, Zhang Z, Zhao X, Hu C, Yang S, Zhou H, Shi J, Shao Z, Xiang Y, Zhu J, Song Y, Zhu J. Efficacy and safety of GLS-010 (zimberelimab) in patients with relapsed or refractory classical Hodgkin lymphoma: A multicenter, single-arm, phase II study. Eur J Cancer. 2022 Mar;164:117-126. doi: 10.1016/j.ejca.2021.07.021. Epub 2021 Aug 27.
PubMed 34462189Loriot Y, Petrylak DP, Rezazadeh Kalebasty A, Flechon A, Jain RK, Gupta S, Bupathi M, Beuzeboc P, Palmbos P, Balar AV, Kyriakopoulos CE, Pouessel D, Sternberg CN, Tonelli J, Sierecki M, Zhou H, Grivas P, Barthelemy P, Tagawa ST. TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes. Ann Oncol. 2024 Apr;35(4):392-401. doi: 10.1016/j.annonc.2024.01.002. Epub 2024 Jan 18.
PubMed 38244927Grivas P, Pouessel D, Park CH, Barthelemy P, Bupathi M, Petrylak DP, Agarwal N, Gupta S, Flechon A, Ramamurthy C, Davis NB, Recio-Boiles A, Sternberg CN, Bhatia A, Pichardo C, Sierecki M, Tonelli J, Zhou H, Tagawa ST, Loriot Y. Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3. J Clin Oncol. 2024 Apr 20;42(12):1415-1425. doi: 10.1200/JCO.22.02835. Epub 2024 Jan 23.
PubMed 38261969
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bladder Preservation With Sacituzumab Govitecan + Zimberelimab for Muscle-Invasive Bladder Cancer in Cisplatin-unfit and Unwilling for Cystectomy Patients: Phase II Trial
- ClinicalTrials.gov ID
- NCT06528483
- Acronym / sponsor ID
- preSAVE / PreSAVE INT 2024
- Conditions
- Bladder Cancer, Bladder Urothelial Carcinoma, Bladder Neoplasm, Muscle-Invasive Bladder Carcinoma
- Keywords
- bladder cancer, muscle-invasive bladder cancer, bladder sparing
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 63 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- 2 Dec 2024 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 30 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with MIBC N0/N1 unwilling or unfit for cystectomy will receive SG + Zimberelimab for 3 cycles of treatment prior of first radiological and TURB re-evaluation.
Patients with stable disease or downstaging will continue Zimberelimab up to 1 year. The goal of this trial is to demonstate that Sacituzumab Govitecan + Zimberelimab can avoid cistectomy and can prolong or avoid recurrence to metastatic disease in selected patients with muscle-invasive bladder cancer.
The primary endpoint of this trial is Event Free Survival that is defined as clinical evidence of new or progressing nodal or any distant metastatic disease, radical cystectomy, or death due to any cause from date of inclusion to the first documentation of a EFS event.
Detailed description
This is an open-label, multi-center, single-group, phase 2 study. Patients with MIBC N0/N1 unwilling or unfit for cystectomy will receive SG + Zimberelimab for 3 cycles of treatment prior of first radiological and TURB re-evaluation.
Approximately 63 patients will be enrolled and assigned to study intervention. At screening, a tumor specimen from TURBT or biopsy done as early as 90 days prior to enrollment will be submitted for central pathology review. All participants will undergo baseline screening imaging (CT or MRI of the chest, abdomen, pelvis) for clinical staging.
Eligible participants will be allocated to study intervention which consist in SG + Zimberelimab for 3 cycles followed by Zimberelimab for 13 cycles in patients who achieve CR/PR/SD at tumor evaluation.
The planned total duration of treatment is approximately 1 year, 3 cycles of SG and 16 cycles of Zimberelimab.
Treatment will be discontinued if the participant experiences unacceptable AE(s), intercurrent illness that prevents further administration of treatment, the investigator's decision to withdraw the participant, the participant withdraws consent, pregnancy of the participant, noncompliance with study intervention or procedure requirements, or the maximum number of cycles has been received for each treatment component individually.
Participants will complete 3 cycles of induction study intervention, followed by repeat imaging studies (same modality as screening) within ≤4 weeks (21 days +/- 7 days) after C3D21 to exclude disease progression. mpMRI/contrast-enhanced or CT scan will assess local invasion by T3 disease or higher and the radiological response to treatment.
Participants who remain radiographically free of distant metastases and PR/SD/CR RECIST v1.1 will proceed to TURBT within 6 weeks of the last dose of SG. TURBT will enable histopathological re-staging and will evaluate pathological response to treatment. The inclusion of bladder muscle in the resection specimen is required. Cystoscopy will be performed before TURBT, as indicated in the Schedule of Activities.
Patients with no evidence of disease at the cystoscopy, will undergo bladder mapping in case of positive urine cytology. In case of negative urine cytology, patients will be considered in as complete respose, in case of no evidence of disease at radiological evaluation.
Participants with radiological progression to metastatic disease or locally advanced disease (from cT2 to cT4 or from N0 to N1), as assessed radiographically, at this time will be considered to have met the primary endpoint of EFS (ie, had an "event") and will not receive further therapy on study, but will transition into survival follow-up and will be treated as per clinical practice.
Participants with pathological downstaging and radiological complete or partial response will continue to receive zimberelimab for 13 cycles (16 cycles as a total) to complete approximately 1 year of total therapy.
Non-responder patients who will maintain radiological or pathological stability will choose to undergo RC or RT/CT or to continue Zimberelimab for 1 years. Additional TURBT could be performed in order to achieve local control, according to the centre clinical practice.
Response to study intervention will be assessed through TURBT and CT SCAN and/or MRI. Imaging should continue to be performed until an EFS event occurs or withdrawal of consent, whichever occurs first. If new anticancer therapy is initiated, this should be documented.
All subjects will be followed for OS every 3 months until death, lost to follow-up, or withdrawal of study consent. Additional survival follow-up may continue for up to 3-5 years from the time of this analysis. To evaluate metastasis free survival, subjects will be monitored by radiographic assessment and cystoscopy on an every-12-week schedule (±5 days). RECIST 1.1 criteria will be used for the assessment. Subjects will be evaluated at every SG + Zimberelimab dose administration plus two additional follow-up visits for safety within the first 100 days from the last dose of study therapy. Beyond 100 days from the last dose of study therapy, subjects will be followed for ongoing drug-related adverse events until resolved, return to baseline or deemed irreversible, or until lost to follow-up, or withdrawal of study consent.
To assess local recurrence, cystoscopy will be performed every 12 weeks (+/- 1 7 days). In case of local recurrence, patients could be managed with TURBT as per clinical practice, in case patients will still be unfit for cystectomy or refuse surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sacituzumab Govitecan + Zimberelimab | Experimental | Drug: Sacituzumab Govitecan + Zimberelimabpatients will be treated with Sacituzumab Govitecan 1,8q21 plus + Zimberelimab q21 for 3 cycles then radiological imaging and TURB will be repeated and patients with Stability of disease or down staging will continue Zimberelimab until disease progression, or unacceptable toxicities or completion of treatment (16 cycles). Patients with progressive disease after 3 cycles of study intervention will be treated as per clinical practice. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Participant is at least 18 years old of age, at the time of providing informed consent.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
- Patients deemed ineligible for Radical Cystectomy (RC) + Retroperitoneal lymphnode dissection (RPNLD) by a urologist and/or oncologist and/or anesthesiology.
- Cisplatin unfit patients as per Galsky criteria (ECOG Performance Status of 2 and/or creatinine-clearance < 60 ml/min and/or CTCAE Gr ≥ 2 hearing loss and/or CTCAE Gr ≥ 2 neuropathy).
Key exclusion criteria (16 listed)
- Positive serum pregnancy test (Appendices 9.4) or women who are breastfeeding.
- Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
- Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section.
- Have had a prior anticancer biologic agent within 4 weeks prior to enrollment or have had prior chemotherapy or targeted small molecule therapy. Patients participating in observational studies are eligible.
- Have previously received topoisomerase 1 inhibitors.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacituzumab Govitecan + ZimberelimabAlso: TRODELVY, AB122Sacituzumab Govitecan 7.5 mg/kg IV for 3 cycles Zimberelimab 360 mg IV for 16 cycles Patients will be treated with Sacituzumab Govitecan 1,8q21 plus + Zimberelimab q21 for 3 cycles then radiological imaging and TURB will be repeated and patients with Stability of disease or down staging will continue Zimberelimab until disease progression, or unacceptable toxicities or completion of treatment (16 cycles). Patients with progressive disease after 3 cycles of study intervention will be treated as per clinical practice. | Drug | Sacituzumab Govitecan + Zimberelimab |
Primary outcome
Event-Free Survival (EFS)
Time frame: 24 months
clinical evidence of new or progressing nodal or any distant metastatic disease, radical cystectomy, or death due to any cause from date of inclusion to the first documentation of a EFS event. Patients last known to be EFS event-free are censored at the date of last event-free cystoscopy and/or CT scan. Those patients without disease assessment who are still alive will be censored at date of inclusion in the trial
6 secondary outcomes
clinical or pathological downstaging
Time frame: 24 months
Number of Participants treated with Pembrolizumab + Enfortumab Vedotin who experience AEs/SAEs
Time frame: 24 months
predictive role of miRNA in patients who achieve clinical or pathological downstaging after SG + Zimberelimab treatment
Time frame: 24 months
predictive role of ctDNA in patients who achieve clinical or pathological downstaging after SG + Zimberelimab treatment
Time frame: 24 months
role of 18FDG-PET in the prediction of response or relapse for N positive patients
Time frame: 24 months
the role of multiparametric MRI (mpMRI) in the assessment of clinical response
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2024.
- Background: PubMed 28279514Bokarica P, Hrkac A, Gilja I. Re: J. Alfred Witjes, Thierry Lebret, Eva M. Comperat, et al. Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. Eur Urol 2017;71:462-75. Eur Urol. 2017 Aug;72(2):e45. doi: 10.1016/j.eururo.2017.02.031. Epub 2017 Mar 6. No abstract available.
- Background: PubMed 35058142Softness K, Kaul S, Fleishman A, Efstathiou J, Bellmunt J, Kim SP, Korets R, Chang P, Wagner A, Olumi AF, Gershman B. Radical cystectomy versus trimodality therapy for muscle-invasive urothelial carcinoma of the bladder. Urol Oncol. 2022 Jun;40(6):272.e1-272.e9. doi: 10.1016/j.urolonc.2021.12.015. Epub 2022 Jan 17.
- Background: PubMed 30482661Royce TJ, Feldman AS, Mossanen M, Yang JC, Shipley WU, Pandharipande PV, Efstathiou JA. Comparative Effectiveness of Bladder-preserving Tri-modality Therapy Versus Radical Cystectomy for Muscle-invasive Bladder Cancer. Clin Genitourin Cancer. 2019 Feb;17(1):23-31.e3. doi: 10.1016/j.clgc.2018.09.023. Epub 2018 Oct 4.
- Background: PubMed 23823157Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. doi: 10.1016/S1470-2045(13)70255-9. Epub 2013 Jul 1.
- Background: PubMed 22512481James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, Crundwell M, Sizer B, Sreenivasan T, Hendron C, Lewis R, Waters R, Huddart RA; BC2001 Investigators. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012 Apr 19;366(16):1477-88. doi: 10.1056/NEJMoa1106106.
- Background: PubMed 32945632Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18.
- Background: PubMed 34861372Powles T, Bellmunt J, Comperat E, De Santis M, Huddart R, Loriot Y, Necchi A, Valderrama BP, Ravaud A, Shariat SF, Szabados B, van der Heijden MS, Gillessen S; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Mar;33(3):244-258. doi: 10.1016/j.annonc.2021.11.012. Epub 2021 Nov 30. No abstract available.
- Background: PubMed 28055103Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
- Background: PubMed 34462189Lin N, Zhang M, Bai H, Liu H, Cui J, Ke X, Zhang H, Liu L, Yan D, Jiang Y, Zang A, Qi J, Wang L, Liu Z, Xu B, Zhang Y, Zhang Z, Zhao X, Hu C, Yang S, Zhou H, Shi J, Shao Z, Xiang Y, Zhu J, Song Y, Zhu J. Efficacy and safety of GLS-010 (zimberelimab) in patients with relapsed or refractory classical Hodgkin lymphoma: A multicenter, single-arm, phase II study. Eur J Cancer. 2022 Mar;164:117-126. doi: 10.1016/j.ejca.2021.07.021. Epub 2021 Aug 27.
- Background: PubMed 38244927Loriot Y, Petrylak DP, Rezazadeh Kalebasty A, Flechon A, Jain RK, Gupta S, Bupathi M, Beuzeboc P, Palmbos P, Balar AV, Kyriakopoulos CE, Pouessel D, Sternberg CN, Tonelli J, Sierecki M, Zhou H, Grivas P, Barthelemy P, Tagawa ST. TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes. Ann Oncol. 2024 Apr;35(4):392-401. doi: 10.1016/j.annonc.2024.01.002. Epub 2024 Jan 18.
- Background: PubMed 38261969Grivas P, Pouessel D, Park CH, Barthelemy P, Bupathi M, Petrylak DP, Agarwal N, Gupta S, Flechon A, Ramamurthy C, Davis NB, Recio-Boiles A, Sternberg CN, Bhatia A, Pichardo C, Sierecki M, Tonelli J, Zhou H, Tagawa ST, Loriot Y. Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3. J Clin Oncol. 2024 Apr 20;42(12):1415-1425. doi: 10.1200/JCO.22.02835. Epub 2024 Jan 23.
- Individual participant dataSharing planned: No
Related trials for Bladder Cancer
Active, not recruitingEarly Phase 1
(CLONEVO): Cell cycLe inhbitiON to Target the EVolution of UrOthelial Cancer
Bladder Cancer
Not yet recruitingObservational study
Outcomes for IR and High Risk (HR) Non-muscle Invasive Bladder Cancer (NMIBC) and ctDNA-based Biomarkers for Response and Recurrence in Muscle Invasive Bladder Cancer (MIBC)
NMIBC, MIBC
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Active, not recruitingPhase 2
Intravesical Gem/Doce in Patients With NMIBC
Urinary Bladder Cancer
Active, not recruitingPhase 3
Testing the Addition of the Anti-cancer Drug, Cabozantinib, to the Usual Immunotherapy Treatment, Avelumab, in Patients With Metastatic Urothelial Cancer, MAIN-CAV Study
Advanced Bladder Urothelial Carcinoma, Advanced Renal Pelvis Urothelial Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giuseppe Procopio, MD principal investigator
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sacituzumab Govitecan + Zimberelimab in people with Bladder Cancer and Bladder Urothelial Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giuseppe Procopio, MD (+ 39 022390 1, giuseppe.procopio@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-Free Survival (EFS) (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06528483, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2024.