Phase 1 N=43 Treatment

Phase Ib Feasibility Trial of Neoadjuvant Nivolumab/Lirilumab in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer

Bladder Cancer

Bottom Line

View on ClinicalTrials.gov: NCT03532451 ↗

Enrolled (actual)

Serious AEs

21.4%

Results posted

Sep 2021

Primary outcome: Primary: Grade 3 or Higher Treatment Related Adverse Events as Assessed by CTCAE V5.0 — 0; 0.07 proportion of participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: Nivolumab (Drug); Nivolumab/Lirilumab (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: PrECOG, LLC.
Primary completion: Nov 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Grade 3 or Higher Treatment Related Adverse Events as Assessed by CTCAE V5.0	0; 0.07	—
SECONDARY Percentage of Participants With Pathologic Complete and Partial Response	16.7; 21.4; 25.0; 32.1	—
SECONDARY Two Year Recurrence-free Survival	82; 89	—
SECONDARY Rate of no RC Due to TRAEs	0; 0	—
SECONDARY Change in CD8+ TIL Density	120.5; 126.9	0.08
SECONDARY Percentage Change in CD8+ TIL Density	0.8; 1.1	0.88

Summary

Patients with muscle-invasive bladder cancer (MIBC) who can not receive cisplatin or refuse cisplatin therapy will receive nivolumab or nivolumab/lirilumab before a planned surgical procedure called a radical cystectomy (RC) to remove the bladder. Nivolumab works by attaching to and blocking a molecule called Programmed Death-1 (PD-1). Lirilumab attaches to and blocks a group of molecules called Killer Cell Immunoglobulin-Like Receptor (KIR). PD-1 and KIR are proteins present mainly on immune system cells, and each controls part of the immune system by shutting it down. It is hoped that by binding to and inactivating these proteins, these drugs can enhance the body's ability to detect, attack and destroy cancer cells. The purpose of this research study is to see whether nivolumab alone or combination of nivolumab and lirilumab given before surgery is effective in treating people who have bladder cancer, and to examine the side effects, good and bad, associated with nivolumab and lirilumab.

Eligibility Criteria

Patients must have histologically confirmed MIBC (T2-T4a, N0-N1, M0 per American Joint Commission on Cancer [AJCC]) pure or mixed histology urothelial carcinoma. Clinical node-positive (N1) patients are eligible provided the lymph nodes (LNs) are confined to the true pelvis and are within the planned surgical LN dissection template.
The most recent TURBT that showed muscularis propria invasion should be within 10 weeks prior to beginning study therapy. Patients must have sufficient baseline tumor tissue from either initial or repeat TURBTs. The local site pathologist will be asked to estimate and record the rough approximate percentage of viable tumor in the TURBT sample (initial or repeat TURBT with highest tumor content) to document at least 20% viable tumor content prior to registration.
Patients must be ineligible for cisplatin-based chemotherapy due to any of the following below OR refused cisplatin-based chemotherapy:
Creatinine clearance(CrCl) <60 mL/min with Easter Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
Creatinine clearance(CrCl) ≥ 60 mL/min with ECOG PS 2 (if patient fit for RC)
Hearing impaired ≥ Grade 2 by CTCAE criteria
Neuropathy ≥ Grade 2 by CTCAE criteria
Patient refused cisplatin-based chemotherapy?
Patients must be medically fit for TURBT and RC.
Age ≥ 18 years.
Ability to understand and willingness to sign Institutional Review Board (IRB)-approved informed consent.
Willing to provide tumor tissue, blood, and urine samples for research.
Adequate organ function as measured by the following criteria, obtained ≤ 4 weeks prior to registration:
Absolute Neutrophil Count (ANC) ≥ 1000/mm³ (stable off growth factor within 4 weeks of first study drug administration)
Platelets ≥ 100,000/mm³
Hemoglobin ≥ 8 g/dL
Serum Creatinine Clearance ≥ 30 mL/min using the Cockcroft-Gault formula
Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3x Upper Limit of Normal (ULN)
Total Bilirubin ≤ 1.5x ULN (in the absence of previously diagnosed Gilbert's disease)
Women must not be pregnant or breastfeeding since we do not know the effects of nivolumab and lirilumab on the fetus or breastfeeding child.
Sexually active women of child-bearing potential with a non-sterilized male partner and sexually active men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the duration of study participation, and for 5 months for women and 7 months for men following last dose of study drugs.
Active or prior documented autoimmune disease within the past 2 years prior to Screening or other immunosuppressive agent within 14 days of study treatment.
Patients may not have locally advanced unresectable or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration.
Patients may not have concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive urothelial carcinoma. Patients with history of non-invasive (Ta, Tis) upper tract urothelial carcinoma that has been definitively treated with at least one post-treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates no evidence of residual disease are eligible.
Patients may not have another malignancy that could interfere with the evaluation of safety or efficacy of the study drugs. Patients with a prior malignancy will be allowed without study chair approval in the following circumstances:
Not currently active and diagnosed at least 3 years prior to the date of registration.
Non-invasive diseases such as low risk cervical cancer or any cancer in situ.
Localized (early stage) cancer treated with curative intent (without evidence of recurrence and intent for further therapy), and in which no systemic chemotherapy was indicated.(e.g. low/intermediate risk prostate cancer, etc.).
Patients may not have received any prior immune checkpo

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Data sourced from ClinicalTrials.gov (NCT03532451). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.