Partners Daiichi Sankyo and Merck & Co. are sharing new phase 2 data for their investigational antibody-drug conjugate, findings the partners think will help score accelerated approval in pretreated small cell lung cancer (SCLC).
“The important take-home message is that this is our registrational trial for the first approval of the drug I-DXd,” Daiichi’s R&D head Ken Takeshita, M.D., told Fierce Biotech Friday.
The primary analysis reveals an objective response rate (ORR) of 48.2% among 137 patients receiving 12 mg/kg of I-DXd, also known as ifinatamab deruxtecan, according to a late-breaking presentation shared at this year’s World Conference on Lung Cancer in Barcelona, Spain.
The ORR is down slightly from the rate seen in an earlier stage of the trial, in which the B7-H3-directed ADC was tied to a 54.8% ORR among 42 patients on the same dose level. Daiichi and Merck reported results from the dose-optimization stage of the phase 2 trial, dubbed IDeate-Lung01, a year ago.
In addition, the latest data demonstrate a median progression-free survival (PFS) of 4.9 months and a median overall survival (OS) of 10.3 months. Again, the figures are slightly down from the previously reported PFS of 5.5 months and OS of 11.8 months from the dose-optimization stage.
“We always get minor fluctuation in these numbers over time, and usually the numbers drift downwards a little bit based from the early data to more mature data,” Takeshita said. “What we see here is typical for most drugs—not just this one—but most drugs from other companies too.”
Takeshita underscored I-DXd’s durability in a population that doesn’t have many treatment options, with the data showing a median duration of response (DOR) of 5.3 months and a disease control rate of 87.6%.
“Traditionally, with these older drugs in small cell lung cancer, responses were good, but patients relapsed pretty quickly,” he explained. “Now, in this trial, what you see is that the duration of responses is reported to be about five [to] six months.”
Previously, two complete responses (CRs) were recorded in the dose-optimization portion of the trial. Now, the companies report one additional CR in the second stage for a total of three.
Among all patients, 63 partial responses (PRs) and 54 cases of stable disease (SD) occurred.
In a subset of 105 patients in the third-line-plus setting, a confirmed ORR of 45.7% was reported. The three CRs occurred in the advanced-setting subpopulation, alongside 45 PRs and 41 cases of SD.
“I wish we could get more of these complete responses in small cell lung cancer trials, and maybe we'll see, eventually, about these combinations with other agents, like the DLL3 bispecific drugs that we are also pursuing,” Takeshita said.
Daiichi and Merck are also working together on two other DXd ADCs, including a DLL3-targeting bispecific T-cell engager dubbed MK-6070. Merck acquired MK-6070 in its $680 million buyout of Harpoon Therapeutics in early 2024. The companies have said that they plan on assessing MK-6070 with I-DXd in certain SCLC patients.
When looking at I-DXd’s safety profile, findings were consistent with those seen in the dose-optimization stage, with no new safety signals reported, according to a Sept. 7 release from Daiichi.
Overall, 89.8% of patients experienced a treatment-related adverse event (TRAE), with 36.5% experiencing a grade 3 or higher event. Thirteen patients (9.5%) had a TRAE associated with treatment discontinuation, while six (4.4%) patient deaths were deemed to be related to treatment.
Considering the advanced nature of the cancer I-DXd is aiming to treat, Takeshita said Daiichi believes the risk-benefit analysis favors the investigational drug.
The presentation also included brain lesion data, with an exploratory analysis of 65 patients with brain metastases at baseline recording an intracranial ORR of 46.2%.
“Most cancer drugs don't have much activity in brain medicine, but this one does for we for reasons which we don't yet know, actually,” Takeshita said. “And so that's very important for patients.”
Daiichi and Merck are already in discussions with regulatory agencies about potential next steps, Takeshita said.
“I'm pretty confident that these data will be sufficient for approval—accelerated approval— in the U.S.,” he said. “If I were the prescribing physician, I think I would say that this is a very nice, important addition to all the drugs that we have available to treat small cell lung cancer. Of course, the list of drugs available to really treat small cell lung cancer that are effective—it's not a long list.”
In mid-August, I-DXd snagged a breakthrough therapy tag from the FDA, a designation that Takeshita said was based on the new phase 2 data. The designation applies to patients with SCLC progression on or after chemotherapy.
Daiichi and Merck are also currently running a phase 3 trial of I-DXd focused on OS, according to Takeshita.
“With limited advances over the last 30 years, there is a high unmet need for new medicines and novel mechanisms of action that could provide additional options to patients with extensive-stage small cell lung cancer,” Eliav Barr, M.D., Merck’s chief medical officer, senior vice president and head of global clinical development, said in the Sept. 7 release.
For Merck, SCLC is one of the tumor types where its blockbuster Keytruda fell short, prompting the pharma to invest in new candidates with the potential to tip the scales in the setting.