Intratumoral injection of CMP-001 in combination with Keytruda (pembrolizumab) worked to reduce tumor burden in advanced melanoma patients whose disease failed to respond, or progressed, when treated with PD-1 inhibitors, data from an ongoing Phase 1 trial show.
These results, of a December analysis in 68 patients, were in the presentation, ‘Intratumoral toll-like receptor 9 (TLR9) agonist, CMP-001, in combination with pembrolizumab can reverse resistance to PD-1 inhibition in a phase Ib trial in subjects with advanced melanoma,” given at the recent AACR annual meeting in Chicago.
The therapy is made of a short piece of DNA, called an oligonucleotide, that mimics the genetic material of bacteria. The DNA is encapsulated in noninfectious virus-like particles, or VLPs, and is injected directly into the tumor — known as intratumoral administration.
VLPs are detected by cells of the immune system that “eat” these particles. The oligonucleotide carried in CMP-001 is then released and processed by a special class of immune cells, called antigen-presenting cells (APCs), which induce a broader immune response and recruit T-cells to the tumor site.
The open-label Phase 1 CMP-001-001 trial (NCT02680184) is investigating the efficacy of intratumoral injection of CMP-001 alone or in combination with Keytruda, another immunotherapy, in patients with advanced melanoma — patients have either failed to respond or progressed when treated with a PD-1/PD-L1 inhibitor like Keytruda.
Set to end in January, it is currently enrolling at sites across the U.S., and the goal is to recruit 160 patients. More information can be found here.
The trial is conducted in two parts — Part 1 has two phases, a dose escalation followed by an expansion phase. Part 2 is designed to assess CMP-001 as a monotherapy.
The escalation phase will assess two dosing schedules of CMP-001 combined with Keytruda: once a week for seven weeks, followed by once every three weeks until discontinuation; or once a week for two weeks, then once every three weeks for five additional doses, after which the therapies are administered once every three weeks until discontinuation.
CMP-001 will be administered at five different doses — 1 mg, 3 mg, 5 mg, 7.5 mg, or 10 mg — directly into a tumor lesion. The response to the combined therapy is evaluated in all tumor lesions, whether or not those lesions were injected with the treatment.
At the time of this analysis, the trial had enrolled 68 patients, all under Part 1: 44 patients in the escalation and 24 patients in the expansion phase.
While 22.5% of the 40 patients receiving the weekly dose experienced a reduction in tumor size (objective response rates, ORR), only 7.7% of the 13 patients receiving the once-every-three-week dosing schedule did.
Patients treated with the 3 mg and 5 mg doses every week had an ORR of 33.3%.
Importantly, tumor lesions throughout the body, namely those in the skin, nodal lymph nodes, spleen and liver that had not been injected with the combo therapy, also showed a regression.
Treatment also increased the recruitment and activation of immune cells into the tumor, namely CD8 T-cells.
Overall, these results show that combining CMP-001 with Keytruda resulted in objective, durable tumor responses without triggering major toxicity issues in PD-1-resistant advanced melanoma patients, the study reports.
Acute adverse effects related to treatment mainly included fever, nausea and/or vomiting, headache, hypotension, and rigors.
“CMP-001 dosing at 5 mg/weekly has been selected for further evaluation in the ongoing dose expansion phase of this study,” the researchers said.