Authorised Therapeutic confirmatory (Phase III) Non-Muscle Invasive Bladder Cancer

CREST - Phase 3 Study of Sasanlimab (PF-06801591) in Combination With Bacillus Calmette-Guerin (BCG) or as a Single Agent in Participants With High-Risk Non-Muscle Invasive Bladder Cancer who do not respond to BCG

EU CTIS ID: 2023-509089-39-00

What this study is testing

BCG-Naïve Cohort (Cohort A) - To demonstrate that PF-06801591 + BCG (induction and maintenance) is superior to BCG (induction and maintenance) in prolonging event-free survival (EFS) in participants with high-risk NMIBC. - To demonstrate that PF-06801591 + BCG (induction) is superior to BCG (induction and maintenance) in prolonging EFS in participants with highrisk NMIBC. BCG-Unresponsive Cohorts (Cohorts B1 and B2) -To estimate the CR rate of PF-06801591 in participants with BCGunresponsive CIS (Cohort B1 only) - To evaluate the EFS of PF-06801591 in participants with BCGunresponsive NMIBC (Cohort B2 only)

Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Participant must be ≥18 years of age, at the time of signing the informed consent (except in Japan, where participants must be ≥20 years).
10. Male or Female Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
11. Capable of giving signed informed consent as described in Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol
Cohorts B1 and B2 only 12. Histological confirmed diagnosis of BCG-unresponsive high-risk, nonmuscle invasive TCC of the urothelium of the urinary bladder defined as any of the following: a) Cohort B1: persistent or recurrent CIS alone or with concomitant recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy. Stage and grade must be confirmed by the BICR prior to registration; b) Cohort B2: recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy; c) Cohort B2: T1 high-grade disease at the first evaluation following an adequate (at least 5 of 6 doses) induction BCG course. It is not required that the participant receive BCG maintenance or a second induction course of BCG per inclusion criterion 13.
Cohorts B1 and B2 only 13. Have received adequate BCG therapy defined as at least one of thefollowing: a) At least 5 of 6 doses of an initial induction course plus at least 2 of 3 doses of maintenance therapy; b) At least 5 of 6 doses of an initial induction course plus at least 2 of 6 doses of a second induction course. Note: The 2 courses described in "a" and "b" should have been administered within a 12 months period (ie the second course started within 12 months from the start of the first course). Note: Additional doses or courses of BCG above the minimum 5 + 2 described in "a" and "b" are allowed, and these do not have to be within the 12 month period. Note: The BCG dose administered in maintenance courses may be 1/2 or 1/3 dose in the event of a BCG shortage, according to NCCN and AUA treatment guidelines. Note: Prior BCG courses must have been comprised ONLY of one or more of the following strains: TICE, RIVM, TOKYO172, IMURON-VAC or Verity BCG (BCG-1), D2PB302, Danish (SSI).
Cohorts B1 and B2 only 14. Have refused or are ineligible for radical cystectomy.

You likely can't join if

1.Evidence of muscle-invasive, locally advanced or metastatic urothelial cancer or concurrent extravesical, non-muscle invasive TCC of the urothelium. For Cohort B1, absence of muscle-invasive and extravesical disease must be confirmed by the BICR prior to registration.
10.Prior radiation therapy to the bladder.
11.Treatment with systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization for participants in Cohort A, or within 4 weeks prior to initiation of study intervention for participants in Cohorts B1 and B2
12.Vaccination with live attenuated vaccines within 4 weeks prior to randomization for participants in Cohort A, or within 4 weeks prior to initiation of study intervention for participants in Cohorts B1 and B2 is prohibited; however, inactivated vaccines are permitted
13.Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
14. Prior/Concurrent Clinical Study Experience Participation in other studies involving investigational drug(s) within 4 weeks prior to randomization; for participants in Cohort A, or within 4 weeks prior to initiation of study intervention for participants in Cohorts B1 and B2.

See the full eligibility criteria

Who can join

1. Participant must be ≥18 years of age, at the time of signing the informed consent (except in Japan, where participants must be ≥20 years).
10. Male or Female Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
11. Capable of giving signed informed consent as described in Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol
Cohorts B1 and B2 only 12. Histological confirmed diagnosis of BCG-unresponsive high-risk, nonmuscle invasive TCC of the urothelium of the urinary bladder defined as any of the following: a) Cohort B1: persistent or recurrent CIS alone or with concomitant recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy. Stage and grade must be confirmed by the BICR prior to registration; b) Cohort B2: recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy; c) Cohort B2: T1 high-grade disease at the first evaluation following an adequate (at least 5 of 6 doses) induction BCG course. It is not required that the participant receive BCG maintenance or a second induction course of BCG per inclusion criterion 13.
Cohorts B1 and B2 only 13. Have received adequate BCG therapy defined as at least one of thefollowing: a) At least 5 of 6 doses of an initial induction course plus at least 2 of 3 doses of maintenance therapy; b) At least 5 of 6 doses of an initial induction course plus at least 2 of 6 doses of a second induction course. Note: The 2 courses described in "a" and "b" should have been administered within a 12 months period (ie the second course started within 12 months from the start of the first course). Note: Additional doses or courses of BCG above the minimum 5 + 2 described in "a" and "b" are allowed, and these do not have to be within the 12 month period. Note: The BCG dose administered in maintenance courses may be 1/2 or 1/3 dose in the event of a BCG shortage, according to NCCN and AUA treatment guidelines. Note: Prior BCG courses must have been comprised ONLY of one or more of the following strains: TICE, RIVM, TOKYO172, IMURON-VAC or Verity BCG (BCG-1), D2PB302, Danish (SSI).
Cohorts B1 and B2 only 14. Have refused or are ineligible for radical cystectomy.
2. Histological confirmed diagnosis of high-risk, non-muscle invasive transitional cell carcinoma (TCC) of the urothelium of the urinary bladder (tumors of mixed transitional/non-transitional cell histology are allowed, but TCC must be the predominant histology) defined as any of the following per World Health Organization grading system. a. T1 tumor b. High-grade Ta tumor c. Carcinoma in situ (CIS)
3. Complete resection of all Ta/T1 papillary disease (including participants with concurrent CIS), with most recent positive TURBT occurring within 12 weeks prior to randomization for participants in Cohort A, or within 12 weeks prior to initiation of study intervention for participants in Cohorts B1 and B2. A second TURBT must have been performed if indicated according to the current locally applicable guidelines, ie, American Urological Association, European Association of Urology.
4. Availability of the tumor tissue from the most recent TURBT for the assessment of the PD-L1 expression. If a second TURBT was performed, as indicated according to the current locally applicable guidelines, the tumor tissue from the TURBT procedure that supports the primary diagnosis for study eligibility should be the tumor tissue used for the PDL1 expression testing.
5. ECOG Performance Status (PS) ≤ 2.
6. Adequate Bone Marrow Function (without hematopoietic growth factor or transfusion support within 14 days prior to study randomization for participants in Cohort A, or within 14 days prior to initiation of study intervention for participants in Cohorts B1 and B2 ), including: a. Absolute neutrophil count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L; b. Platelets ≥100,000/mm3 or 100 x 109/L; c. Hemoglobin ≥9 g/dL (≥5.6 mmol/L).
7. Adequate renal function defined by an estimated creatinine clearance ≥30 mL/min according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance, or according to local institutional standard method.
8. Adequate liver function, including: a. Total serum bilirubin ≤1.5 × the upper limit of normal range (ULN). Participants with Gilbert syndrome who should have total serum bilirubin <3 x ULN; b. Aspartate and alanine aminotransferase (AST and ALT) ≤ 2.5 × ULN.
9. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.

What rules you out

1.Evidence of muscle-invasive, locally advanced or metastatic urothelial cancer or concurrent extravesical, non-muscle invasive TCC of the urothelium. For Cohort B1, absence of muscle-invasive and extravesical disease must be confirmed by the BICR prior to registration.
10.Prior radiation therapy to the bladder.
11.Treatment with systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization for participants in Cohort A, or within 4 weeks prior to initiation of study intervention for participants in Cohorts B1 and B2
12.Vaccination with live attenuated vaccines within 4 weeks prior to randomization for participants in Cohort A, or within 4 weeks prior to initiation of study intervention for participants in Cohorts B1 and B2 is prohibited; however, inactivated vaccines are permitted
13.Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
14. Prior/Concurrent Clinical Study Experience Participation in other studies involving investigational drug(s) within 4 weeks prior to randomization; for participants in Cohort A, or within 4 weeks prior to initiation of study intervention for participants in Cohorts B1 and B2.
15.Cohort A: Known or documented absolute and/or relative contraindication of adjuvant intravesical BCG treatment: a. Prior BCG sepsis or systemic infection (including current urinary tract infection) b. Total bladder incontinence defined as use more than 6 pads in 24 hours c. Adverse experience to previous BCG instillation that resulted in treatment discontinuation or precludes re-treatment.
2.Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Participants with diabetes type I, vitiligo, psoriasis, or hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
3.Severe active infections including pulmonary tuberculosis requiring systemic therapeutic oral or IV antibiotics within 2 weeks prior to randomization for participants in Cohort A, or within 2 weeks prior to initiation of study intervention for participants in Cohorts B1 and B2. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection) are eligible.
4.Other malignancy within 5 years prior to randomization for participants in Cohort A, or within 5 years prior to initiation of study intervention for participants in Cohorts B1 and B2, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance without any plans for treatment intervention (eg, surgery, radiation, or castration) or other concurrent malignancy the investigator feels has a very low likelihood to become metastatic after discussion with the sponsor.
5.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
6.Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C - eg, presence of hepatitis B surface antigen [HBsAg] or positive hepatitis C antibody test result at screening or within 3 months prior to randomization for participants in Cohort A, or within 3 months prior to initiation of study intervention for participants in Cohorts B1 and B2) is acceptable if the participant otherwise meets entry criteria.
7.Cohort A: Intravesical BCG therapy within 2 years prior to randomization. Cohorts B1 and B2: Any systemic or intravesical chemotherapy or immunotherapy from the time of most recent positive TURBT to initiation of study intervention (single-dose intravesical chemotherapy as part of the most recent positive TURBT according to the current locally applicable guidelines is allowed). Prior intravesical chemotherapy for NMIBC is allowed in all Cohorts.
8.Prior immunotherapy with anti PD-1, anti PD-L1, anti PD-L2, or anti cytotoxic Tlymphocyteassociated antigen-4 (CTLA-4) antibody.
9.Prior treatment with immunostimulatory agents including interleukin (IL)-2, IL-15, interferon (INF)-gamma.

The study team makes the final eligibility decision.

Where it's taking place

Korea, Republic of
China
Australia
Canada
United States
Russian Federation
United Kingdom
Japan

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Korea, Republic of; China; Australia; Canada; United States; Russian Federation and 2 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.