UPDATED: Amgen's tarlatamab BiTEs at small cell lung cancer in brief readout

Amgen is claiming phase 2 victory for its prioritized bibispecific T-cell engager (BiTE), saying tarlatamab spurred durable response rates in patients with small cell lung cancer. 

The news, announced in Amgen’s second-quarter earnings report, was short but sweet, with the Los Angeles pharma reporting that the DLL3-targeting asset “demonstrated a durable objective response rate” in patients with relapsed or refractory small cell lung cancer who had advanced after two or more prior lines of therapy. Amgen says the response rate “substantially exceeds what was previously reported in the phase 1 study” and that no new safety signals have arisen. David Reese, Amgen's R&D chief, lauded the data on the company's earnings call.

"I think it represents what we had hoped to see in the BiTE platform," he said. "I couldn't be more pleased with the response rate data, the duration in response and overall survival. 

The data was described as “potentially registrational” by Amgen as the company prepares to meet with regulators to discuss next steps. A spokesperson declined to say whether the discussions will include a potential accelerated approval, saying that Amgen “wouldn’t get into specifics at this time about our conversations with regulatory bodies.” More is expected to be announced at an upcoming medical conference, the spokesperson added. 

A phase 3 trial comparing tarlatamab to chemotherapy as second-line therapy in patients with small cell lung cancer is continuing to enroll. Amgen expects to launch two more late-stage trials in earlier-line patients as well. 

Previous data from an open-label phase 1 trial published at the beginning of the year found that tarlatamab spurred a 23.4% objective response rate with a median response lasting just more than a year. The disease control rate was 51.4% among the 107 evaluable patients that received tarlatamab. 

An editorial from two thoracic oncologists from Memorial Sloan Kettering Cancer Center published in April noted that while the objective response rate was similar to that of available treatments, the duration of response and percent of patients reporting a response at data cutoff was “exceptional.” Amgen reported that 44% of responders had an ongoing response at the cutoff. One of the editorial authors, Charles Rudin, M.D., has previously been a paid consultant for Amgen. 

But the safety profile in the early-stage study was less than stellar, with treatment-emergent side effects impacting all 107 treated patients and more than half of those reporting serious side effects. The most common side effect was cytokine release syndrome, impacting 52.3% of patients. Grade 3 or greater neurologic events were reported in 12 patients, and two patients discontinued treatment due to neurologic side effects. Reese said Thursday that Amgen has "learned a lot" about the clinical management of tarlatamab but that he was "quite pleased" with the rate of side effects like cytokine release syndrome. The safety and tolerability profile in the phase 2 trial was described as better than what was reported in the earlier study but Amgen did not release specifics.

Tarlatamab has emerged as one of Amgen’s best bets among a suite of BiTE molecules, which includes FDA-approved Blincyto. A year ago, the company cut BCMA- and PSMA-targeting molecules, with Reese saying tarlatamab would be a priority moving forward. Four additional phase 1 BiTE molecules remain in the pipeline. 

Editor's note: This story was updated with comments from Amgen's second-quarter earnings call.