On October 6, 2020 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that the University of Louisville and the Ochsner Clinic in New Orleans, Louisiana are now active trial sites in its Phase 1/2 Actimab-A venetoclax combination trial for patients with Relapsed or Refractory ("R/R") Acute Myeloid Leukemia ("AML") age 18 and above (Press release, Actinium Pharmaceuticals, OCT 6, 2020, View Source [SID1234568155]). These sites join UCLA Medical Center, where the trial is being led by Gary Schiller, MD, Professor, Hematology-Oncology and Director, Hematologic Malignancy/Stem Cell Transplant Program. Both sites participated in Actinium’s Phase 2 trial with Actimab-A as a single agent that produced remission rates as high as 69% with minimal non-hematologic toxicities in patients newly diagnosed with AML. The Phase 2 trial results together with a synergistic mechanism of action with venetoclax demonstrated in pre-clinical studies are driving this combination trial with an initial focus on the high unmet needs of R/R patients including those who have relapsed or do not respond to treatment with venetoclax based regimens.

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"Venetoclax is now a mainstay in the AML treatment armamentarium, but the lack of durable remissions, particularly in patients with relapsed or refractory disease who may not respond to venetoclax at all, is an area we are committed to addressing. Our pre-clinical data indicate that Actimab-A is synergistic with venetoclax in venetoclax-resistant cell lines and have documented a reduction of Mcl-1 as the mechanism. Our clinical trial seeks to demonstrate improved response rates and response durations without added toxicities with the combination of Actimab-A and venetoclax. Given the preclinical data, the targeted nature of Actimab-A, and the minimal non-hematologic toxicity profile, we think that the combination with venetoclax has great promise" said Dr. Mark Berger, Actinium’s Chief Medical Officer. Dr. Berger added, "We are delighted to once again be working with the University of Louisville and the Ochsner Clinic who were among the top enrolling sites in our Phase 2 single-agent Actimab-A trial. We look forward to activating additional sites on this important trial as we work to advance treatment options for patients with AML."

Actinium recently announced that the first dose cohort in the Phase 1 portion of the Actimab-A venetoclax combination trial has been complete and enrollment of the second dose cohort has been initiated. Actinium expects continued site additions and anticipates proof of concept results from the Phase 1 portion of the trial in 2021.

Rationale for Actimab-A Venetoclax Combination Trial

This Phase 1/2 trial is a multicenter, open label trial of Actimab-A (lintuzumab-Ac225) added to venetoclax for patients with CD33 positive relapsed/refractory (R/R) Acute Myeloid Leukemia. In a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, Actimab-A was shown to be synergistic with venetoclax in venetoclax resistant cell lines, by depleting MCL-1, a protein shown to mediate resistance to venetoclax. The Phase 1 portion of the study is designed to determine the maximum tolerated dose (MTD) of Actimab-A added to venetoclax for R/R AML. The Phase 2 portion of the trial will assess the percentage of patients with Overall Response (CR + CRh) up to six months after the start of the treatment without receiving other AML therapies. The trial will enroll R/R AML patients who have been treated with venetoclax as well as venetoclax-naïve patients. At the 1.0 uCi/kg dose, Actimab-A is administered on Day 5 of each cycle for four cycles and venetoclax is taken on Days 1-21 of each cycle for up to 4 cycles. Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery. Gary Schiller, MD, Professor, Hematology-Oncology and Director, Hematologic Malignancy/Stem Cell Transplant Program at the UCLA Medical Center is the Principal Investigator for this study.