Highlighting Key Developments in Clinical and Strategic Thinking From Web-Based Sources


Newsworthy, Late-breaking Information from Web-based Sources, Professional Societies and Government Agencies

FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma

The Food and Drug Administration has granted approvals to nivolumab and ipilimumab (Opdivo and Yervoy) in combination for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC). Approvals were based on CheckMate 214 (NCT02231749), a randomized open-label trial. Patients with previously untreated advanced RCC received nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks for 4 doses followed by nivolumab monotherapy (3 mg/kg) every 2 weeks, or sunitinib 50 mg daily for 4 weeks followed by 2 weeks off every cycle.
The trial demonstrated statistically significant improvements in overall survival (OS) and objective response rate (ORR) for patients receiving the combination (n=425) compared with those receiving sunitinib (n=422). Estimated median OS was not estimable in the combination arm compared with 25.9 months in the sunitinib arm (hazard ratio 0.63, 95% CI: 0.44, 0.89; P<0.0001). The ORR was 41.6% (95% CI: 36.9, 46.5) for the combination versus 26.5% (95% CI: 22.4, 31) in the sunitinib arm (P<0.0001). The recommended schedule and dose for this combination is nivolumab, 3 mg/kg, followed by ipilimumab, 1 mg/kg, on the same day every 3 weeks for 4 doses, then nivolumab, 240 mg, every 2 weeks or 480 mg every 4 weeks.

Peloton Therapeutics initiates phase 2 trial of oral HIF-2α inhibitor PT2977 for treatment of von Hippel-Lindau Disease-associated kidney cancer

Peloton Therapeutics, Inc., announced dosing of the first patient in a Phase 2 trial evaluating the efficacy and safety of lead investigational oncology agent, PT2977, to treat von Hippel-Lindau (VHL) disease-associated kidney cancer. PT2977 is a once-daily, oral inhibitor of HIF-2α, a transcription factor that has been implicated in the development and progression of RCC. The primary objective of the Phase 2 trial is to evaluate the efficacy of PT2977 for the treatment of VHL disease-associated renal tumors as measured by overall response rate. Secondary objectives include duration of response, time to response, progression free survival, and time to surgery for VHL disease-associated renal tumors. The trial will also evaluate the efficacy of PT2977 in other VHL disease-associated tumor types as well as the safety and pharmacokinetics of PT2977. Patients will be evaluated radiologically approximately every 12 weeks while continuing in the study.
Peloton’s drug discovery and development efforts focus on identifying novel compounds capable of modulating complex protein-protein interactions that drive disease which have eluded conventional small molecule approaches. Peloton has the only clinical stage small-molecule inhibitors of HIF-2α, and PT2977 has demonstrated a favorable profile in a Phase 1 study in patients with advanced solid tumors including RCC. The study will enroll 50 patients at clinical trial centers across the United States and Europe. More information about the trial is available at www.clinicaltrials.gov, identifier NCT NCT03401788.

First patient enrolled in phase 1 trial of INCB01158, Keytruda combo for solid cancers

The first patient has been treated in a Phase 1 clinical trial evaluating a combination of INCB01158 (aka CB-1158) plus Keytruda (pembrolizumab) in patients with advanced solid tumors, including RCC. The trial is evaluating the safety and effectiveness of INCB01158, given alone or in combination with an anti-PD-1 immune checkpoint inhibitor like Keytruda. Developed by Calithera in collaboration with Incyte Corporation, INCB01158 is an immunotherapy that targets selectively the arginase enzyme.
Arginase is an enzyme produced in the tumor micro-environment by immunosuppressive cells, like myeloid-derived suppressor cells (MDSCs). Its activity depletes the amino acid arginine, which is essential for immune T-cells to proliferate and survive. Inhibiting arginase is thus expected to promote the T-cell expansion at the tumor site in cancers where arginase-secreting MDSCs are known to play an immunosuppressive role. These include renal cell cancer, breast cancer, lung cancer, and acute myeloid leukemia.
Because INCB01158 increases the amount of T-cells within the tumors, researchers believe it might work in synergy with other immunotherapies that unleash T-cells’ tumor-killing functions.
The Phase 1 trial (NCT02903914) is designed to assess the safety of INCB01158 and define a recommended dose to be used in planned Phase 2 studies, both as a monotherapy and in combination with immune checkpoint therapy. The study is being conducted in the U.S. and is expected to include 236 patients with advanced or metastatic solid tumors. Enrollment is ongoing.

Delayed mRCC targeted therapy does not worsen survival

SAN FRANCISCO—Delayed rather than early initiation of targeted therapy (TT) following cytoreductive nephrectomy for metastatic renal cell carcinoma (mRCC) is not associated with worse survival, according to findings presented at the American Urological Association 2018 annual meeting. In a retrospective observational study that included 2716 patients with mRCC treated with both cytoreductive nephrectomy and TT, Solomon Woldu, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues found that the risk of death among patients with moderately delayed, delayed, and late TT did not differ significantly from patients who had early TT.
The investigators defined TT delivered within 2 months of mRCC diagnosis as early (1255 patients, 46.2%). They considered TT delivered in 2 to 4 months, 4 to 6 months, and more than 6 months to be moderately delayed (1072 patients, 39.5%), delayed 284 patients, 10.5%), and late (105 patients, 3.9%), respectively. The median time from mRCC diagnosis to initiation of TT was 2.1 months.
The investigators acknowledged that their study is limited by the study design and potential selection bias, but noted that the findings are consistent with the idea that, among carefully selected patients, initial observation might not compromise outcomes.

Partial vs radical nephrectomy lowers elderly patient mortality risk

SAN FRANCISCO—Compared with radical nephrectomy (RN), partial nephrectomy (PN) for small renal tumors in elderly patients is associated with a lower risk of cancer-specific and other-cause mortality, researchers reported at the American Urological Association 2018 annual meeting.
Using 2004–2014 data from the Surveillance, Epidemiology and End Results (SEER) registry, Michele Marchioni, MD, of SS Annunziata Hospital “G.D’Annunzio” University of Chieti, Chieti, Italy, and colleagues identified 4541 surgically treated patients aged 75 years or older who had non-metastatic pT1a renal cell carcinoma. After they matched 1 RN to 1 PN patient by propensity score, the investigators had a study cohort of 2826 patients.
In multivariate analysis, PN was associated with a sig-”nificant 36% and 33% decreased risk of cancer-specific and other-cause mortality, respectively. The investigators found no difference in 30-day mortality risk. The authors concluded that PN should be given strong consideration in the treatment of small renal tumors, even for elderly patients.

Global kidney cancer drugs market forecast for 2017-2025

DUBLIN—The global kidney cancer drug market was valued at US$ 3,302.3 million in 2016, and is expected to reach US$ 6,441.9 million by 2025, expanding at 8.1% from 2017 to 2025, according to data from ResearchAndMarkets.com
The incidence of renal cell cancer is observed highest in Northern America and Europe. Almost 59% of kidney cancer cases are observed in developed countries. Thus, rising incidence of kidney cancer and entry of novel drug treatments are the key factors contributing to the growth of the kidney cancer drug market. Sutent dominates the global kidney cancer/renal cell carcinoma drugs market. North America dominates the global kidney cancer drugs market followed by Europe.
Rise in incidence of renal cancer, increasing geriatric population and novel drug treatment are key drivers for the growth of the kidney cancer drug market in North America. Asia Pacific is the fastest growing regional market for kidney cancer drugs with the highest compound annual growth rate in the forecast period. Improvements in diagnostic technology, a rise in aged population and low cost production of drugs are some of the key factors contributing to the growth of the market in the Asia Pacific region. KCJ