Jedd Wolchok, MD, PhD
“THIS IS a wonderful presentation and a very exciting trial,” said formal discussant Jedd Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York. Despite the remarkable advances achieved with anti–programmed cell death protein 1 and ligand 1 (anti–PD-1/anti–PD-L1) treatment, “there are patients who are primarily refractory or respond and become resistant to anti–PD-1 and anti–PD-L1,” Dr. Wolchok reminded listeners. “We have much to do.”
“We are now assembling a list of features that we think confer resistance to anti–PD-1 and anti–PD-L1,” he continued. One of these mechanisms is a cold/desert-like noninflamed phenotype, referred to as an “immune desert,” a term based on tumor biopsies. Patients with preexisting immunity (ie, immune infiltrate) can respond, whereas tumors devoid of immune infiltrate [“immune desert”] are those that don’t respond, he continued.
This is where interventions such as CMP-001 come in. “CMP-001 focuses on improving antigen presenting cell function. You can’t induce a tumor-specific immune response without an activated antigen-presenting cell,” he said. “The study suggests the number of plasmacytoid dendritic cells might be an active biomarker.”
“It appears that CMP-001 can mobilize immune activity in a few days by virtue of this initial TLR stimulus. The durable response is probably due to immune priming. Response rates are excellent, and the abscopal effect is what we would hope to see. Adverse events were manageable. I applaud the translational studies and look forward to more detailed data,” Dr. Wolchok said. “CMP-001 appears to be able to turn a desert into an oasis,” he added. ■
DISCLOSURE: Dr. Wolchok reported no conflicts of interest.
COMBINING CMP-001, a Toll-like receptor 9 (TLR9) agonist, plus pembrolizumab (Keytruda) appears to overcome resistance to anti–programmed cell death protein 1 (anti–PD-1) therapy, according to a preliminary phase Ib study.1 Adding CMP-001 to pembrolizumab was well tolerated, with antitumor efficacy ...