St. Joseph Heritage Medical Group

1563 Background: Clinical trials that require patients to have specific actionable mutations based on next generation sequencing (NGS) present unique problems, such as recruiting patients with rare mutations, low enrollment rates, and distance between patients and trial sites. Such barriers can slow the pace of trial enrollment and delay the development of new therapeutic options. Methods: Tempus Labs has partnered with experienced research sites and pharmaceutical companies with molecularly targeted clinical trials to create the TIME Trial Network. The study portfolio includes pharmaceutical sponsored phase I-III clinical trials across solid tumors and hematological malignancies, targeting actionable mutations. This network was established to ensure rapid just-in-time (JIT) activation of trials by streamlining start-up activities (i.e., execution of CTAs and study budgets/financial exhibits, regulatory paperwork, SIV planning and conduct, drug and study supply shipments, submission to the central IRB, and sponsor-specific requirements). Rapid activation begins upon receipt of an activation form from a site partner. “Site Activated” describes a site that has fulfilled all regulatory, documentation, contracting requirements, and has sponsor approval to screen and enroll patients. Results: In Q4 2020, JIT activations were completed for 6 unique interventional clinical trials across 10 sites in 8 US states in the TIME Trial Network. On average, sites were activated in 9.4 business days. Patients enrolled had rare NGS mutations and were from geographically diverse locations. In one urgent case, trial activation, patient consent, screening, and treatment were achieved in 5 business days. In total, 91.7% of patients consented to trial. The average timeline from activation to consent was 4.5 days (range 0 - 24 days), with half of patients consenting within 1 business day. 45.5% of patients who consented to trial received the study drug within 1 day of consent; 2 patients dosed on day of consent. Conclusions: Over a 3-month period, on average, TIME Trial sites were activated in 9.4 days (compared to the 20+ week industry-wide average), and patient consent was completed in 4.5 days. Rapid JIT activations through the TIME program provide significant improvements in trial enrollment timelines and increase access to therapies nationwide. JIT activations may be especially useful for rural, underserved communities, as sites can enroll diverse patient populations and help address the equity gap in clinical trials across ethnic groups.[Table: see text]

Abstract The purpose of this study is to evaluate the safety and preliminary efficacy of a targeted immunotherapy for breast cancer based on SV-BR-1-GM, a breast cancer cell line modified to secrete GM-CSF. The regimen used includes low dose cyclophosphamide (300 mg/m2) 2-3 days prior to inoculation to reduce immune suppression; irradiated SV-BR-1-GM (20,000 cGy) dosed intradermally (ID) in 4 sites (~20x106 cells total); and post-inoculation interferon-α (10,000 units ID into the SV-BR-1-GM inoculation sites) 2±1 and 4±1 days later. Dosing is every 2 weeks for the first month, then monthly for up to one year. This regimen was used in a prior study in 4 evaluable patients with advanced cancer (3 breast and 1 ovarian) and was safe and well tolerated. One patient, who had a partial response of widely metastatic breast cancer, was found to match SV-BR-1-GM at an MHC class II allele (HLA-DRB3*02:02). This regimen is being used in a clinical trial (NCT03066947 in ClinicalTrials.gov) in patients with advanced breast cancer. To date 7 patients with metastatic breast cancer have been recruited and 6 dosed with evidence of tumor response in 2 patients. Ages ranged from 46-73. Time from initial diagnosis ranged from 2 - 12 years. The number of prior chemotherapy or biological therapy regimens ranged from 3-7. Treatment was generally safe and well tolerated. The majority of adverse events were limited to local irritation at the injection sites. No serious adverse events related to SV-BR-1-GM treatment have been reported and no new or unexpected safety issues related to SV-BR-1-GM have been observed. Two patients dropped out after a single cycle of treatment. One patient with inflammatory breast cancer dropped out after 2 treatments due to worsening breast inflammation. One patient appeared to be responding in the breast after the first treatment, with regression of soft tissue lesions in the breast, but developed a worsening pleural and pericardial effusions shortly after the second treatment with the development of pulseless electrical activity and was unable to be resuscitated. One patient has received 5 cycles of therapy and is ongoing. One patient had a notable response. For this 73-year-old woman with breast cancer diagnosed in 1995 with liver and lung metastases and 7 prior rounds of chemotherapy, after 3 months of treatment her scans noted “a clear response in the multiple bilateral pulmonary nodules” indicating that several lung tumors had disappeared or decreased in size. This response was maintained after 6 months. The liver tumors were stable to slightly increased at 3 months, and then progressed after 6 months. This patient matched with SV-BR-1-GM at 2 HLA loci (HLA-A*24:02 and HLA-DRB3*02:02). The regimen used in this study has shown early evidence of activity in these patients with late stage, heavily pre-treated metastatic breast cancer. HLA matching may be useful in predicting those patients most likely to respond. Citation Format: Jarrod P. Holmes, Elizabeth Tan-Chiu, Charles L. Wiseman, Markus D. Lacher, George Peoples, William V. Williams. Safety and efficacy of a whole-cell targeted immunotherapy for breast cancer: Preliminary findings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT171.