FDA Fast Tracks Treatment for for Select Stage IIB to IV Malignant Melanoma

The FDA has awarded fast track designation to KIN-2787 as a potential treatment for patients with BRAF class II or III alteration-positive and/or NRAS mutation-positive, metastatic or unresectable, stage IIB to IV malignant melanoma.¹ The drug has previously been granted FDA orphan drug designation for patients with stage IIB-IV melanoma.

A phase 1 trial (NCT04913285) is analyzing the tolerability, safety, pharmacokinetics, and efficacy of the novel treatment in adults with BRAF-mutated, advanced or metastatic solid tumors (n = 155).²

To be eligible for enrollment, patients must have had measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 to 2, and acceptable organ function. Patients must also be able to swallow, retain, and absorb oral medications.

The investigators noted that approximately 6% of patients with cancer harbor oncogenic BRAF alterations, which have been shown to lead to activated BRAF monomers (class I), homodimers (class II), and heterodimers (class III).

Although BRAF inhibitors have been approved for patients with class I BRAF mutation-driven cancers, these medications have not shown efficacy in patients with class II or III mutations. In the dose-escalation portion of the trial, patients with solid tumors with class I, II, or III mutations were administered KIN-2787 monotherapy. The researchers are seeking to determine the recommended dose of the drug for the phase 2 portion of the clinical program.

The dose-expansion is comprised of 3 cohorts, with each expected to enroll 25 patients. The first group enrolled patients with melanoma carrying class II or III BRAF alterations.

Patients are being administered KIN-2787 at a twice-daily dose of 25 mg/kg in 28-day treatment cycles. The second group is enrolling patients with non-small cell lung cancer and class II or III BRAF alterations.

The third group includes patients with other solid tumors with class II or III BRAF alterations. These patients were also administered KIN-2787 at 25 mg/kg twice daily.

The trial’s primary end points include incidence of dose-limiting toxicities, treatment-emergent adverse effects (AEs), treatment-related AEs, and incidence of clinically significant changes in vital signs, physical examinations, electrocardiograms, and clinical laboratory tests.

In the dose-expansion part of the program, primary end points include evaluating objective response rate, disease control rate, duration of response, and duration of stable disease across cohort. Key secondary end points include maximum observed plasma concentration (Cmax) of KIN-2787, time to achieve Cmax, and area under the plasma concentration time curve.

References

1. Kinnate Biopharma Inc. receives fast track designation from the US Food and Drug Administration for KIN-2787, an investigational pan-RAF inhibitor. News release. Kinnate Biopharma, Inc. September 21, 2022. Accessed September 26, 2022. https://bit.ly/3Rg11BB

2. Franovic A, Miller N, Severson P, et al. The next-generation pan-RAF inhibitor, KIN-2787, is active in class II and class III BRAF mutant models. J Clin Oncol. 2021;39(suppl 15):3116. doi:10.1200/JCO.2021.39.15_suppl.3116