Melanoma Shrinks With Injection After Anti-PD-1 Progression

Intratumoral injection of a toll-devour receptor (TLR) agonist showed ability for reversing PD-(L)1 resistance in melanoma, a preliminary scientific trial showed.

A filled with 23.5% of patients with metastatic melanoma answered to intratumoral CMP-001 and systemic pembrolizumab (Keytruda), including seven full responses. All of the patients had disease progression or proper disease within the midst of prior anti-PD(L)-1 therapy.

The results moreover showed that noninjected lesions regressed following the therapy, suggesting abscopal antitumor exercise, Mohammed Milhem, MD, of the University of Iowa in Iowa Metropolis, reported within the midst of a press briefing that preceded the Society for Immunotherapy of Most cancers virtual assembly.

“Intratumoral CMP-001 plus pembrolizumab reversed resistance to PD-1 blockade and resulted in sturdy, systemic responses in patients with developed melanoma and prior disease progression on anti-PD-1 therapy,” he acknowledged. “Systemic responses to CMP-001 plus pembrolizumab have been observed with an identical imply regression of injected and noninjected aim lesions. CMP-001 alone and in combination with pembrolizumab modified into smartly tolerated, with basically the most traditional therapy-connected detrimental occasions being low-grade flu-devour symptoms and injection-situation anxiety.”

A member of the virtual viewers puzzled whether on the least some patients would possibly perchance perchance perchance moreover just need answered to pembrolizumab monotherapy.

“All patients had obtained on the least 12 weeks of therapy with the PD-1 inhibitor and had demonstrated that their tumors have been rising,” acknowledged Milhem. Nonetheless, affirmation of progression modified into no longer required within the glimpse however will be required in an ongoing trial of the mix.

“If you occur to gave one other 4 to 6 weeks of pembrolizumab, we would wonder if there would possibly perchance perchance perchance be a response or no longer,” he acknowledged.

Greater than 90% of the glimpse participants had revolutionary disease, versus proper disease, Milhem added.

Even supposing checkpoint inhibitors have revolutionized therapy of developed melanoma, patients who progress within the midst of or after therapy have few effective alternatives. CMP-001 features a TLR9 agonist within an immunogenic virus-devour particle (VLP) that induces anti-VLP antibodies and stimulates plasmacytoid dendritic cells to stimulate interferon-alpha induction. In preclinical items, the make increased tumor regression as when compared with a make that disregarded the TLR9 agonist.

Milhem reported findings from a trial racy patients with metastatic nonuveal melanoma and lesions amenable to intratumoral injection. In the end of the dose-escalation/expansion hiss of the trial, 159 patients obtained CMP-001 and pembrolizumab. Investigators evaluated two dosing schedules for CMP-001: as soon as weekly for 7 weeks or 2 weeks, adopted by further dosing every 3 weeks till therapy discontinuation. In the end of a preplanned 2d portion of the trial, 40 patients obtained CMP-001 most provocative.

In the end of the dose-escalation/expansion section, 98 patients obtained CMP-001 with a polysorbate 20 (PS20) focus of 0.01%, and 61 obtained CMP-001 with a PS20 focus of 0.00167%.

The key aims of the trial have been to determine the urged section II dose and schedule of CMP-001 in combination with pembrolizumab (portion 1) and to determine the safety of single-agent CMP-001 monotherapy (portion 2). Secondary aims integrated safety and antitumor exercise of the mix and single-agent CMP-001.

Patients who obtained the mix with the upper focus of PS20 had a twofold better response fee, 23.5% vs 11.5%. Overall, 23 of 98 patients had just responses with the upper focus of PS20 versus eight of 61 within the group that obtained the decrease focus. Total responses occurred in seven patients and one affected person, respectively, within the two groups. An further 16 of the 98 patients had proper disease versus 18 of 61.

The CMP-001 monotherapy group had an just response fee of 17.5% (seven of 40 patients), all partial responses. An further 13 patients had proper disease. Responses have been much less sturdy with single-agent CMP-001 (median of 5.6 months) versus the mix (19.9 months).

An evaluation of 22 patients with each injected and noninjected aim lesions showed that some extent of tumor shrinkage occurred in all noninjected aim lesions, and tumor shrinkage exceeded 30% in 20 of the 22 circumstances. In different circumstances, the degree of tumor shrinkage in noninjected lesions exceeded that of the injected lesions, including some patients whose injected lesions did now not regress.