Phase 12 Study of Mebendazole plus Radiation in

Phase 1/2 Study of Mebendazole plus Radiation in Patients with Recurrent Meningioma Grade 2 or 3 Soma Sengupta MD, Ph. D. , Stacey Worrell, MPH & Gregory Riggins, MD, Ph. D. * University of Cincinnati & Johns Hopkins University* NRG Oncology Virtual Summer Meeting July 16 -18, 2020 @NRGOnc NRG Oncology

Mebendazole A chance discovery identifies anticancer activity in an anti-helminthic leading to two clinical trials for brain cancer. • Fenbendazole used to treat pinworms prevented tumor engraftment in our mouse colony. • This prompted a search for related drugs approved for human use. • Mebendazole is FDA approved for anthelminthic use. • Mebendazole is regarded as safe and sold over the counter in tropical countries including Australia and Brazil.

Mebendazole: Preclinical evidence

Mebendazole Phase 1 for High Grade Glioma

Mebendazole Phase 1 for Pediatric Brain Cancer

Study Design This is a dual institution, open label, nonrandomized phase 2 with a phase 1 lead in trial to determine the safety and efficacy of mebendazole given in combination with radiation (any modality) in recurrent meningiomas grade II or III at mebendazole oral doses between 50 to 100 mg/kg/day.

Treatment Plan • Patients must have clinical and/or MRI confirmation of recurrent, or progressive meningioma grade 2 or 3 and be a candidate for radiotherapy of any modality. • Mebendazole will be taken two days prior to the start of radiation therapy and will continue post radiation for a total of 24 months or documented progression. • The starting dose of mebendazole will be at 50 mg/kg/day, then the dose will increase to 100 mg/kg/day after standard 3+3 dose escalation. • If 100 mg/kg/day is not tolerated, treating physician has the option to reduce dosing to an intermediate level of 75 mg/kg/day.

Acknowledgements Brain Tumor Biology and Therapy Laboratory at Johns Hopkins (preclinical) Gregory Riggins, MD Ph. D- Laboratory Director griggin 1@jhmi. edu Alex Yamashita- IDH 1 mutant tumors Marina de Costa Rosa- IDH 1 mutant glioma Natalie Joe- Mebendazole and Breast Cancer Tara Williamson- Cancer prevention, animal models, drug combinations, lab manager Michelle Abreu (alumni)-cancer prevention Thais Biude (alumni)- Thyroid Cancer Renyuan Bai (assoc. prof) - liposomal, mebendazole and bacteriolytic therapy University of Cincinnati Soma Sengupta MD, Ph. D. , - Clinical Trial PI Stacey Worrell, MPH- Statistics Funding Past and Present to preclinical work: National Institutes of Health (NCI, NINDS), The Virginia and D. K. Ludwig Fund for Cancer Research, The Center for Disease Control jointly with NIOSH, Florence and Irving Sherman Neurosurgery Research Professorship, ABC 2, Cures within Reach, Peter Jennison, Leonard and Phyllis Attman, The Jeffery Williams Memorial Gift Fund, Margaret H. Riggins, Col. James Riggins (USAF, Ret. ), & George Riggins. @NRGOnc NRG Oncology