First-in-Human phase II clinical trial of Multiplex Intra Tumoral Immunotherapy (MITI) with RPT-01-5001 in patients with metastatic solid cancer (Abscopal 5001Trial)

Abstract:

Background: Little is known of the synergy of combination intratumoral immunotherapy and cancer ablation. We undertook a Phase II Trial (Abscopal 5001; NCT04713371) for patients with metastatic solid cancer to assess the safety and efficacy of cryoablation with concurrent injection of RPT-01-5001 (combination of low-dose checkpoint inhibitors and chemotherapy), a treatment process referred to as Multiplex Intratumoral Immunotherapy (MITI^TM).

Methods: Twelve patients with metastatic cancer who had failed standard therapy and one with sacral chordoma received at least one intratumoral treatment of MITI, preceded by 3-5 days of oral low-dose cyclophosphamide. MITI consisted of CT-guided cryoablation followed by intratumoral injection of RPT-01-5001. In addition, GM-CSF was subcutaneously administered daily for a total of 4 weeks. Treatment was repeated every 4 weeks if tumor burden remained stable or reduced as noted by iRECIST criteria.  These criteria were modified when follow-up biopsies revealed pathology with minimal or no cancer despite persistent suspicious mass(es) on imaging.

Results: Cancers included prostate (4 patients), sarcoma (2), and 1 each of breast, colon, bladder, uterine cervix, tongue, kidney, and sacral chordoma. Eight patients received 3 cycles of treatment, two received 2, and three received 1. All patients tolerated the procedure well and were discharged within 2 hours. Adverse event rate was 69%, all of which were Grade 1 or 2, except for two Grade 3 with delayed cryosurgical complication of transient pneumothorax (15%). At completion of up to 3 cycles of treatment, partial response (iPR) was observed in 5 patients (38.5%) and stable disease (iSD) in 5 (38.5%), for a disease control rate (iDCR) of 77%. Disparity between post-treatment imaging and pathologic findings was observed in 4 patients (positive vs. negative, respectively), requiring modification of the iRECIST criteria in favor of pathology. Best response ranged from 0-91%, with a mean for responding patients of 38%. Median progression-free survival (PFS) and 95% confidence intervals (95% CI) were 5.4 months (1.8 to 23.1 months); median overall survival (OS) was 20.9 months (9.1 to 22.8 months). Injection site response was observed in 9 (69%), and distal abscopal effect was seen in 4 (31%), including one sarcoma and one bladder cancer patient with complete abscopal response of lung metastases; biopsy-confirmed resolution of liver metastases was also noted in the bladder cancer patient.

Conclusions:  MITI with RPT-01-5001 is safe and highly feasible, providing 77% disease control and 31% abscopal effect in patients with metastatic cancer who have failed standard therapy.

Biography:

Dr. David G. Bostwick, MD, MBA is founder and Chief Executive Officer of Rampart Health. He is internationally renowned, with over 45 years of experience and interest in prostate cancer, bladder cancer and urologic diseases. He has previously held appointments at the National Cancer Institute, Stanford University, University of Chicago, University of Maryland, and Mayo Clinic. In 1999, he founded Bostwick Laboratories and grew it into the largest and most profitable medical laboratory focused on urologic pathology in the US and UK, with revenue topping $175 million at peak; the Company was purchased in 2011. Dr. Bostwick has authored 18 books, more than 25 book chapters, and more than 475 professional papers . He has presented more than 2000 lectures around the world, and has served as Principal Investigator or Co-Investigator for more than 10 clinical trials.