AACR: Monday’s Stars Include Affimed, Hoth and Blueprint
The American Association for Cancer Research (AACR) Annual Meeting is running from April 7-13 in New Orleans, with hundreds of presentations on cutting-edge cancer research. The presentations run the gamut from preclinical studies to late-stage clinical trials. Here’s a look at some of the preclinical and early-stage studies recently presented.
Purple Biotech’s CM24 Against Solid Tumors
Israel’s Purple Biotech presented favorable interim safety and efficacy data from its Phase Ib trial of CM24 in multiple solid tumors. CM24 is a humanized monoclonal antibody that blocks CEACAM1, a novel immune checkpoint protein that supports tumor immune evasion and survival by leveraging multiple pathways. The drug is being evaluated in combination with Bristol Myers Squibb’s anti-PD-1 checkpoint inhibitor Opdivo (nivolumab).
The primary objective of the trial is safety, tolerability, PK and determining the appropriate dose for the Phase II trial. No dose-limiting events were observed across all dose levels. To date, the best overall response included one confirmed partial response (PR) in a pancreatic cancer patient and three with a disease control rate of 36%, two with pancreatic cancer and one with papillary thyroid cancer.
Affimed’s Innate Cell Engager in Hodgkin and Non-Hodgkin Lymphomas
Germany’s Affimed provided a data update on the ongoing Phase I/II trial of AFM13 precomplexed with cord blood-derived natural killer (cbNK) cells. The trial is being run at The University of Texas MD Anderson Cancer Center in patients with CD30-positive relapsed or refractory Hodgkin and non-Hodgkin lymphomas. The data demonstrated a 100% objective response rate (ORR) and an improvement of complete response (CR) rate to 62% at the recommended Phase II dose in 13 patients after two cycles of therapy. The treatment was well tolerated with no cases of cytokine release syndrome, immune effector cell-associated neurotoxicity or graft versus host disease.
Nouscom’s Off-the-Shelf Cancer Vaccine
Switzerland’s Nouscom presented encouraging new translational data from its ongoing Phase I study of NOUS-209. NOUS-209 is an off-the-shelf cancer vaccine that targets 209 shared neoantigens. It is being dosed with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) in patients with Microsatellite Instable High (MSI-H) gastric, colorectal and gastro-esophageal junction solid tumors. The new data suggest the therapy is safe and highly immunogenic, and it demonstrated promising efficacy signals.
“While we have seen progress in the treatment options for MSI-High solid tumors in recent years, there remains a significant unmet need,” said Dr. Marwan G. Fakih, M.D., medical oncology specialist at City of Hope, Duarte, California, and study investigator. “It is therefore extremely encouraging to see this new translational Phase I data illustrating how NOUS-209 induces robust T cell expansion and TCR diversification in patients demonstrating durable clinical responses.”
Hoth Therapeutics’ Antisense Oligonucleotide
New York-based Hoth Therapeutics provided an update on its HT-KIT. HT-KIT is a chemically-stable antisense oligonucleotide that targets the proto-oncogene KIT by frameshifting KIT mRNA transcriptions. Hoth evaluated it on mast cell leukemia cells in vitro and observed reduced KIT protein expression, signaling and function. Treating with the therapy prevented cancer cell growth and induced cell death over 72 hours. In a humanized mast cell leukemia mouse model, tumor growth and metastases were reduced while tumor cell death was increased. Even though the data was all preclinical, company shares jumped 135% at the news.
Robb Knie, Hoth’s chief executive officer, said, “Our next round of preclinical studies are underway and we are excited to utilize the results for our planned Pre-IND meeting with FDA later this year.”
Surface Oncology’s IL-27 Antibody
Cambridge, Massachusetts-based Surface Oncology presented new preclinical and translational data for SRF388. The drug is a first-in-class antibody targeting IL-27. It also reported PK data from the dose-escalation phase of the SRF388 Phase I trial, which showed no dose-limiting toxicities.
“We are very pleased to share the compelling preclinical and translational data that enabled us to select the dose for our Phase II trials of SRF388,” said Dr. Alison O’Neill, M.D., Surface’s chief medical officer. “These data add to the growing body of evidence supporting our belief that IL-27 is a highly immunosuppressive cytokine that serves as a critical regulator of checkpoint protein expression, and treatment with SRF388 shuts down IL-27 signaling.”
Blueprint Achieves Proof of Concept in NSCLC
Cambridge, Massachusetts-based Blueprint Medicines presented proof-of-concept data from the Phase I/II SYMPHONY trial of BLU-945 for advanced EGFR-mutant non-small cell lung cancer (NSCLC). BLU-945 was designed to provide broad coverage of common activating and on-target resistant mutations, spare wild-type EGFR and other kinases to limit off-target toxicities, and prevent treating CNS metastases. Early data from the ongoing Phase I SYMPHONY trial demonstrated dose-dependent decreases in circulating tumor DNA (EGFR variant allele fractions) and radiographic tumor reductions, including a PR in a patient who received 400 mg once a day, the highest dose tested. The drug was generally well-tolerated with no significant adverse events related to wild-type EGFR inhibition.
“The initial BLUE-945 data reported today, which highlight its potential to address resistance to current standard of care therapies including Osimertinib and enable well-tolerated, broad-acting combinations, are an important step forward toward improving outcomes for patients with EGFR-mutant lung cancer,” said Dr. Elaine Shum, M.D., assistant professor in the department of medicine and a medical oncologist at NYU Langone Health’s Perlmutter Cancer Center, and an investigator on the SYMPHONY trial.