Guru Sonpavde, MD, director of Bladder Cancer at Dana-Farber Cancer Institute, discusses immunotherapy combination studies for the treatment of patients with urothelial carcinoma.

There is an ongoing, phase III, first-line study investigating durvalumab (Imfinzi) plus tremelimumab versus gemcitabine platinum-based chemotherapy versus durvalumab alone.

Additionally, one study is investigating ipilimumab (Yervoy) plus nivolumab (Opdivo) in the first-line setting of advanced urothelial carcinoma, comparing it with gemcitabine and cisplatin. There is a substudy investigating gemcitabine cisplatin plus or minus nivolumab in cisplatin eligible patients.

In a phase I/II study investigating the combination, the objective response rate for patients receiving nivolumab at 1 mg/kg with ipilimumab at 3 mg/kg (N1/I3; n = 26) was 38.5% (95% CI, 20.2-59.4), with a complete response rate of 3.8%. In patients receiving nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg (N3/I1; n = 104), the ORR was 26% (95% CI, 17.9-35.5) and the CR rate was 2.9%.

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Dr. Sonpavde on Immunotherapy Combination Studies in Urothelial Carcinoma

Guru Sonpavde, MD, director of Bladder Cancer at Dana-Farber Cancer Institute, discusses the phase IIIb safety study of fixed-dose durvalumab (Imfinzi) and tremelimumab in patients with advanced urothelial carcinoma during the 2018 Genitourinary Cancers Symposium.

The open-label, multicenter STRONG study is enrolling approximately 1200 patients with advanced disease in patients during or following nonplatinum or platinum-based therapy. What is novel about this study, Sonpavde says, is that patients receive durvalumab at a fixed-dosing schedule. In the study that led to durvalumab's May 2017 FDA approval in urothelial carcinoma, the single-arm phase I/II Study 1108, patients were treated with a weight-based dosing regimen of 10 mg/kg every 2 weeks.

This study includes separate cohorts of patients with durvalumab alone at a fixed-dose schedule of 1500 mg every 4 weeks. This is a flat dosing regardless of weight, he adds, which was seen in earlier studies to provide the same pharmacokinetics as weight-based dosing.

Once the durvalumab monotherapy cohort is established, investigators will study this fixed dose of durvalumab in combination with tremelimumab, which will also be given at a fixed dose every 4 weeks. 

Guru Sonpavde, MD, director of Bladder Cancer at Dana-Farber Cancer Institute, discusses a phase IIIb safety study of fixed-dose durvalumab (Imfinzi) and tremelimumab in patients with advanced urothelial carcinoma.

Dr. Sonpavde on Fixed-Dose Durvalumab and Tremelimumab Study in Urothelial Carcinoma

Guru Sonpavde, MD, director of Bladder Cancer at the Dana-Farber Cancer Institute, discusses ongoing trials investigating immunotherapy for patients with penile cancer.  

There are exciting trials investigating PD-1 inhibitors, explains Sonpavde. Pembrolizumab (Keytruda) is being studied in the post-platinum setting in a phase II trial (NCT02837042). Once eligibility is confirmed, patients will start treatment cycles with pembrolizumab at 20 mg given intravenously on the first day of each cycle. Each cycle corresponds to a duration of 3 weeks.  

The primary outcome of this trial is objective tumor response rate from baseline up to 2 years, progression-free survival, overall survival, and the safety profile. 

Additionally, ipilimumab (Yervoy) is being studied in combination with nivolumab (Opdivo). This combination is being looked at in all rare cancers in a basket trial.  

Guru Sonpavde, MD, director of Bladder Cancer at the Dana-Farber Cancer Institute, discusses ongoing trials investigating immunotherapy for patients with penile cancer.

Dr. Sonpavde on Ongoing Trials With Immunotherapy for Penile Cancer

Guru Sonpavde, MD, director of Bladder Cancer at the Dana-Farber Cancer Institute, discusses the potential for immunotherapy in penile cancer.

There is promise for PD-1 checkpoint inhibitors, as well as CTLA-4 plus PD-L1 combination strategies in the treatment of patients with penile cancer, says Sonpavde.

Sonpavde says that he expects activity with immunotherapy regimens because PD-L1 is overexpressed in over 50% of tumors, and about 50% of patients have disease derived from HPV.

Dr. Sonpavde on the Potential for Immunotherapy in Penile Cancer

Guru Sonpavde, MD, director of Bladder Cancer at the Dana-Farber Cancer Institute, discusses current clinical trials in penile cancer.

EGFR is overexpressed at the protein and gene expression level, and has gene amplification at the DNA level in penile cancer, making it a target, says Sonpavde.

In the HER family of inhibitors, there was a trial with dacomitinib that was recently published, showing a response rate in the first-line neoadjuvant setting of about 32%. And afatinib (Gilotrif) is being looked at in the post-platinum salvage setting.

Additionally, pembrolizumab (Keytruda) is being investigated in the post-platinum setting, and the combination of ipilimumab (Yervoy) plus nivolumab (Opdivo) is being investigated all rare cancers.

Guru Sonpavde, MD

Articles

Dr. Sonpavde on Immunotherapy Combination Studies in Urothelial Carcinoma

Dr. Sonpavde on Fixed-Dose Durvalumab and Tremelimumab Study in Urothelial Carcinoma

Dr. Sonpavde on Ongoing Trials With Immunotherapy for Penile Cancer

Dr. Sonpavde on the Potential for Immunotherapy in Penile Cancer

Dr. Sonpavde Discusses Current Clinical Trials in Penile Cancer