On December 15, 2021 Exelixis, Inc. (Nasdaq: EXEL) reported initiation of the dose-escalation stage of STELLAR-002, a phase 1b trial evaluating XL092 in combination with immuno-oncology therapies in advanced solid tumors (Press release, Exelixis, DEC 15, 2021, View Source [SID1234597193]). The objective of the study is to evaluate the safety, tolerability and efficacy of XL092, Exelixis’ novel next-generation tyrosine kinase inhibitor (TKI), in combination with: nivolumab (OPDIVO); nivolumab and ipilimumab (YERVOY); and nivolumab and bempegaldesleukin.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Exelixis is sponsoring STELLAR-002, and Bristol-Myers Squibb Company (NYSE: BMY) is providing nivolumab, ipilimumab and bempegaldesleukin for use in the trial, in accordance with their clinical trial collaboration and supply agreement announced in June. Nektar Therapeutics (Nasdaq: NKTR) will supply bempegaldesleukin to Bristol Myers Squibb through their existing global development and commercialization collaboration.

"The initiation of the dose-escalation stage of STELLAR-002, our second phase 1b trial of XL092, is an important step toward evaluating the potential of this next-generation tyrosine kinase inhibitor in combination with three additional immuno-oncology therapies for patients with advanced genitourinary tumors," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer, Exelixis. "We are pleased to continue our successful collaboration with Bristol Myers Squibb through this trial and look forward to identifying the recommended doses for the cohort-expansion stage."

The dose-escalation stage will determine the recommended dose in patients with advanced solid tumors for each of the XL092 combination therapy regimens. Once the recommended dose is established, the trial will begin to enroll tumor-specific expansion cohorts for patients with advanced renal cell carcinoma, urothelial carcinoma and metastatic castration-resistant prostate cancer. The primary efficacy endpoint of the expansion stage will be objective response rates, except for the cohort of patients with metastatic castration-resistant prostate cancer, for which the primary endpoint will be duration of radiographic progression-free survival.

About XL092

XL092 is a next-generation oral tyrosine kinase inhibitor that targets kinases implicated in cancer growth and spread, including VEGF receptors, MET, AXL and MER. In designing XL092, Exelixis sought to build upon its extensive experience with cabozantinib, the company’s flagship medicine, retaining the target profile while improving key characteristics, including pharmacokinetic half-life. XL092 is currently being developed for the treatment of advanced solid tumors, including genitourinary cancers, as a monotherapy and in combination with immune checkpoint inhibitors. XL092 is the first internally discovered Exelixis compound to enter the clinic following the company’s reinitiation of drug-discovery activities.

About Genitourinary Cancers

Genitourinary cancers are those that affect the urinary tract, prostate, testicles or penis — parts of the body involved in reproduction and urine production and excretion — and include renal cell carcinoma (RCC), castration-resistant prostate cancer (CRPC) and urothelial carcinomas.1

The American Cancer Society’s (ACS) 2021 statistics cite kidney cancer as among the top 10 most commonly diagnosed forms of cancer among both men and women in the U.S.2 Clear cell RCC is the most common type of kidney cancer in adults.3 Papillary RCC accounts for about 15% of all renal cell cancers.4,5 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.2 Approximately 32,000 patients in the U.S. and over 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021, with nearly 15,000 patients in need of a first-line treatment in the U.S.6
According to the ACS, in 2021, approximately 250,000 new cases of prostate cancer will be diagnosed, and 34,000 people will die from the disease.2 Prostate cancer that has spread beyond the prostate and does not respond to androgen-suppression therapies — a common treatment for prostate cancer — is known as metastatic CRPC.7 Researchers estimate that in 2020, 43,000 people were diagnosed with metastatic CRPC, which has a median survival of less than two years.8,9,10
Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.11 Bladder cancer occurs mainly in older people, with 90% of patients aged 55 or older.12 With an estimated 84,000 new cases expected to be diagnosed in 2021, bladder cancer accounts for about 5% of all new cases of cancer in the U.S. each year.2,13 It is the fourth most common cancer in men.2