Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer (NILE)

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Metastatic Urothelial Cancer; Unresectable Locally Advanced Urothelial Cancer

Treatments: Drug: Cisplatin + Gemcitabine; Drug: Carboplatin + Gemcitabine; Drug: Durvalumab; Drug: Tremelimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03682068

2018-001883-48 (EudraCT Number)

D933SC00001

Details and patient eligibility

About

This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of combining durvalumab ± tremelimumab with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra).

Enrollment: 1,246 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
• Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
• At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
• Adequate organ and marrow function as defined in the protocol
• Life expectancy ≥12 weeks in the opinion of the investigator
• Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

Key Exclusion Criteria:

• Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
• No severe concomitant condition that requires immunosuppression medication
• Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
• Patients who may be eligible for or are being considered for radical resection during the course of the study.
• Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,246 participants in 3 patient groups

Durvalumab in Combination with SoC Chemotherapy

Experimental group

Description:

Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine

Treatment:

Drug: Durvalumab

Drug: Carboplatin + Gemcitabine

Drug: Cisplatin + Gemcitabine

Durvalumab in Combination with Tremelimumab+SoC Chemotherapy

Experimental group

Description:

Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks Tremelimumab will be provided for 4 cycles. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine

Treatment:

Drug: Tremelimumab

Drug: Durvalumab

Drug: Carboplatin + Gemcitabine

Drug: Cisplatin + Gemcitabine

SoC Chemotherapy

Active Comparator group

Description:

Patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine

Treatment:

Drug: Carboplatin + Gemcitabine

Drug: Cisplatin + Gemcitabine