Nuvalent has reported phase 1/2 lung cancer data, teeing the biotech up to talk to the FDA about an approval filing that could establish its neladalkib as a challenger to Pfizer’s Lorbrena.
The ALKOVE-1 trial enrolled patients with advanced ALK-positive non-small cell lung cancer (NSCLC). These patients currently start on Roche’s Alecensa, switch to Pfizer’s Lorbrena when they progress and have few options for third-line treatment. Nuvalent has designed the tyrosine kinase inhibitor (TKI) neladalkib to address the resistance and safety problems of existing TKIs and to work across any line of therapy.
Nuvalent reported a 31% response rate among 253 patients with advanced ALK-positive NSCLC who had previously received any prior ALK TKI. In the study's primary analysis population, patients had received a median of three prior lines of therapy, with 51% having previously received chemotherapy.
The study was yet to reach the median duration of response (DOR) after 11.3 months of follow-up. After six months, 76% of responses were ongoing. The figure fell to 64% after 12 months and 53% after 18 months.
Almost 80% of patients had received at least two ALK TKIs and 91% of participants had taken Lorbrena. The lack of effective drugs in the third-line population means there is no relevant cross-trial benchmark. Nuvalent reported a 49% response rate and 14.4-month median DOR in patients with ALK mutations and prior Lorbrena use in the phase 1 part of the trial.
Nuvalent also shared data from 63 patients who hadn’t received Lorbrena. The results will shape the biotech’s attempts to replace Pfizer’s drug as the preferred second-line treatment. The response rate was 46% and the trial was yet to reach the median DOR. After six months, 89% of responses were ongoing. The figure fell to 80% after 12 months and 60% after 18 months.
Guggenheim Securities analysts said in a note to investors last month that Lorbrena won approval for post-Alecensa use based on a response rate of around 40% and DOR of about seven months. Nuvalent executives told the analysts they were focused more on DOR than response rate, given the potential for the patient mix to influence the latter endpoint.
“Management’s thesis was that neladalkib should drive more prolonged durability compared to [Lorbrena] on cross-trial comparison. Their goal isn’t to be marginally better, but meaningfully better so that it is a black-and-white comparison,” the analysts said.
Nuvalent’s plan for wresting market share from Pfizer relies on neladalkib being more durable and less toxic than Lorbrena. The biotech said increases in two liver enzymes, which were seen in 44% and 47% of patients, were the most frequent treatment-emergent adverse events (TEAEs). At the phase 2 dose, TEAEs caused dose reductions in 17% of patients and treatment discontinuation in 5% of participants.
Nuvalent plans to discuss the data with the FDA at a pre-new drug application meeting. While Nuvalent is initially targeting the TKI pretreated, ALK-positive NSCLC population, the biotech is running a phase 3 trial to establish neladalkib in TKI-naïve patients. The phase 3 trial is pitting neladalkib against Alecensa.
The biotech shared data from an exploratory cohort of 44 TKI-naïve patients who were enrolled in the phase 1/2 trial. In this group, Nuvalent reported an 86% response rate and a 9% complete response rate. Two of the 38 responders had progressed as of the data cutoff.