March 8, 2021:

Big Ten Cancer Research Consortium investigators presented a virtual poster highlighting BTCRC-GU16-043, a Big Ten CRC phase Ib/II study of durvalumab and guadecitabine in advanced kidney cancer, during the 2021 Genitourinary Cancers Symposium.

The study, led by the University of Michigan Rogel Cancer Center, investigates whether adding guadecitabine, a drug that targets DNA methylation, might increase the proportion of patients with advanced clear cell renal carcinoma (ccRCC) who respond to treatment with durvalumab, a checkpoint inhibitor that targets the PD-1/PD-L1 pathway.

In the Phase Ib portion of the study, which enrolled 6 subjects, the maximum tolerated dose of guadecitabine was determined to be 45mg/m2 per day. Investigators reported pooled toxicity and efficacy data for 42 checkpoint inhibition (CPI)-naïve subjects from phase Ib and phase II. An exploratory cohort was enrolling up to 16 additional subjects at the time of presentation.

Study authors concluded guadecitabine in combination with durvalumab was well tolerated and had reasonable activity in first-line advanced ccRCC. Additionally, myeloid-derived suppressor cells (MDSCs) and T lymphocytes decreased among responders, and increased Th17 subpopulations of T cells were associated with immune-mediated toxicities. Researchers are continuing to study this combination in CPI-refractory RCC.

Authors included: Yousef Zakharia1, Eric A. Singer2, Ryan Ross3, Monika Joshi4, Michael Abern5, Rohan Garje1, Joseph J. Park3, Ilona Kryczek3, Weiping Zou3, and Ajjai Shivaram Alva31University of Iowa, 2Rutgers Cancer Institute of New Jersey, 3University of Michigan, 4Penn State Cancer Institute, 5University of Illinois at Chicago.

“From an efficacy standpoint, the overall response rate was about 22%, and all were partial responses,” said Dr. Zakharia, a medical oncologist at the Holden Comprehensive Cancer Center at the University of Iowa. “More importantly, we encountered a significant number of patients whose disease was stabilized. About 60% had stable disease that lasted more than six months and median progression-free survival of 17.5 months.”

Dr. Alva, sponsor-investigator of the study and a medical oncologist at the University of Michigan Rogel Cancer Center, said further exploration to improve tumor response is needed.

“The improvement we’re trying to achieve is in making more of these kidney tumors responsive to immunotherapy and that’s an ongoing process with other potential targets on the radar,” he said.

Dr. Alva noted this is the second successful advanced RCC trial conducted through the Big Ten Cancer Research Consortium; the first (BTCRC-GU14-003), was published in the Journal of Clinical Oncology last year.

“Logistically, this combination is a little more challenging because guadecitabine has to be injected subcutaneously for five days in a row,” Dr. Alva said. “We were able to complete this comprehensive study with very few deviations, in spite of COVID. This speaks to the resilience of the Big Ten Cancer Research Consortium and its ability to execute complicated studies at a high-quality level.”

The study is supported by AstraZeneca Pharmaceuticals, LP, and Astex Pharmaceuticals, Inc.

See abstract.


About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research Consortium is to create a unique team-research culture to drive science rapidly from ideas to new approaches to cancer treatment. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer.

About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 14 Big Ten institutions will provide over $200 million in direct financial support to more than 9,800 students for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women, including the addition of men’s ice hockey and men’s and women’s lacrosse since 2013. For more information, visit