FDA Grants Fast Track Designation to CMP-001 Combination in Advanced Melanoma

The FDA has granted Fast Track designation to CMP-001 in combination with nivolumab (Opdivo) plus ipilimumab (Yervoy), which will undergo clinical trial development both as a potential extender of time to disease relapse as an initial treatment of patients with unresectable stage III or stage IV melanoma, as well as to improve the overall tumor response rate as treatment of patients with unresectable or metastatic melanoma refractory to prior anti-PD-1 blockade.¹

Before this regulatory action, CMP-001 was granted Orphan Drug designation for IIB/IV melanoma.

“These FDA designations for CMP-001 are testaments to the critical need for new drugs designed to treat patients with melanoma,” said Barry Labinger, CEO of Checkmate. “We look forward to continued engagement with the FDA in advancing the development of CMP-001 in combination with PD-1 blockade in melanoma and head and neck squamous cell carcinoma.”

In a phase 1B clinical trial, CMP-001 combined with pembrolizumab (Keytruda) elicited durable responses in patients with PD-1 resistant metastatic melanoma, according to results presented during the 2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting.²

The objective response rate (ORR) observed with CMP-001/pembrolizumab was 25% (95% CI, 16%-36%) among patients who were given the 0.01% PS20 formulation of the investigational drug. Responses included 6 complete responses (CRs) and 15 partial responses (PRs). Notably, a total of 4 patients who continued study treatment after disease progression eventually achieved a CR or PR. Among the 61 patients who received the 0.00167% PS20 formulation of CMP-001, the ORR was 11.5%.

According to a Kaplan Meier estimate, the median duration of response (mDOR) in this study was 16.8 months (95% CI, 5.8-not reached [NR]). The estimated mDOR among the 28 patients who had a response to treatment was 25.2+ months (95% CI, 8.6-NR), and this included the patients who responded after disease progression.

The ongoing multicenter, 2-part, open-label trial (NCT02680184) continues to evaluate the efficacy and safety of intratumoral CMP-001 as monotherapy or in combination with pembrolizumab in patients with PD-1 resistant melanoma. In the dose-escalation phase, CMP-001 at dose levels of 1 mg, 3 mg, 5 mg, 7.5 mg, and 10 mg were administered to 44 patients. Pembrolizumab was added as either 1 injection per week for 7 weeks followed by every 3 weeks or 1 injection per week for 2 weeks followed by every 3 weeks. The dosing patterns for pembrolizumab were continued until treatment discontinuation.

In the dose-expansion portion of the study, CMP-011 is administered at a dose level of either 5 or 10 mg in 69 patients. The trial also includes a second dose-expansion phase in which patients received 10 mg of CMP-001, along with a higher concentration formulation of the investigational agent.

All study treatment is continued until disease progression or unacceptable toxicity. Treatment can also be discontinued per investigator’s decision or withdrawal of consent from the patient receiving treatment.

The target enrollment for the study is 199 patients, and the study is no longer accruing patients. Individuals with PD-1 resistant advanced melanoma were eligible to enroll in the study with a histopathologically confirmed diagnosis of this disease, an ECOG performance status of 0 or 1, a life expectancy of at least 24 weeks, measurable disease, and adequate bone marrow, renal function, liver function, and laboratory values. Patients were required to have received prior anti-PD-1 therapy.

In the study, patients who received CMP-001 monotherapy and did not respond were able to cross over to the combination arm.

CMP-001 is a CpGA DNA Toll-like receptor9 agonist with the ability to activate tumor-associated plasmacytoid dendritic cells to produce interferon, which in turn induces antitumor systemic immunity. Nivolumab plus ipilimumab is an anti-PD1 regimen that has shown prior promise in advanced melanoma in the CheckMate 067 clinical trial (NCT01844505).¹

With an FDA Fast Track designation, Checkmate Pharmaceuticals, the developer of CMP-001, could be eligible for frequent meetings with the FDA, which may ultimately lead to a Priority Review of a Biologics License Application or New Drug Application.

_References:

_{Checkmate Pharmaceuticals granted fda fast track designation for cmp-001 combined with pd-1 blockade in the treatment of certain types of metastatic or unresectable melanoma. News release. Checkmate Pharmaceuticals. July 27, 2020. Accessed July 27, 2020. https://bwnews.pr/2P0mPDF}

_{Kirkwood J, Milhem M, Zakharia Y, et al. Durable responses in anti-PD-1 refractory melanoma following intratumoral injection of Toll-like receptor 9 (TLR9) agonist CMP-001, in combination with pembrolizumab. Presented at: 2019 Annual Meeting of the Society for Immunotherapy of Cancer. November 6-10, 2019: National Harbor, MD.}