ASH: Seagen's Adcetris and Bristol's Opdivo boost hopes for another ADC, PD-1 combo

If you can’t beat them, join them.

After Bristol Myers Squibb’s Opdivo topped Seagen’s classical Hodgkin lymphoma (cHL) therapy Adcetris in a head-to-head trial, Seagen has trotted out new datasets suggesting the two drugs—a PD-1 inhibitor and an antibody-drug conjugate—hold potential when paired together as part of a combination.

In a midstage study, all patients with early-stage cHL who received a combination of Adcetris, Opdivo and the chemotherapy regimen AD (doxorubicin and dacarbazine) were alive without disease progression one year after treatment. The analysis came from 150 patients enrolled in part C of the phase 2 SGN35-027 trial and was shared at the 65th American Society of Hematology annual meeting.

The data look promising, but cHL is known to be relatively easy to treat. In an interview, Megan O’Meara, M.D., Seagen’s head of clinical development, acknowledged that people want to see longer-term data—and ultimately a survival benefit—in frontline cHL. At 18 months, 3% of patients in the trial had developed progressive disease.

Seagen had previously shared a 98% tumor response rate among the 150 patients, including 93% with no sign of tumor at the end of treatment. But the progression-free survival information is new.

On Adcetris’ home turf, advanced cHL, SGN35-027 part B linked the Adcetris-Opdivo-AD regimen to a 95% overall response rate among 56 patients, with 89% being complete responders. About 88.3% of patients were alive without disease worsening after two years.

The data were drawn from a median follow-up of 24.2 months. The numbers were better than the 93% overall response rate and 88% complete response rate Seagen reported last year.

Investigators didn’t spot any unexpected safety signals from the new combo, and the regimen is considered tolerable, O’Meara noted. Across both cohorts, about a third of patients developed grade 3 or above adverse events that were deemed treatment-related, with elevated liver enzymes and neutropenia occurring most frequently

Seagen currently sees the data as proof of principle for future studies of a “potentially promising regimen with less chemotherapy,” O’Meara said.

Adcetris, a CD30-targeted ADC, is currently approved by the FDA in frontline advanced-stage cHL alongside a chemo combo called AVD. With the new regimen, Seagen is trying to replace the vinblastine chemo component with Opdivo. As for early-stage cHL, the idea of being able to remove radiation—which may cause long-term side effects—for a younger patient population is very appealing for physicians, O’Meara explained.

The updated readouts come a few months after Opdivo beat Adcetris in the phase 3 SWOG S1826 trial. The BMS immunotherapy significantly reduced the risk of cancer progression or death by 52% compared with Adcetris in their respective AVD combinations in first-line advanced-stage cHL.

Pairing with Opdivo could be a potential solution for Adcetris to avoid a market showdown, although without a head-to-head trial, it’s not clear whether the novel combo works better than the Opdivo-AVD regimen.

Despite the encouraging data from SGN35-027 so far, Seagen hasn’t started a randomized trial testing the Opdivo-Adcetris-AD combo.

“I think we’re still at this point following the data and looking at multiple options and opportunities for next steps,” O’Meara said. “But we’re happy with the regimen, both from a safety and an efficacy perspective.”

If Seagen's reluctance to launch a late-stage trial stems from spending concerns, that factor could be resolved in the near future.

Seagen is currently being acquired by Pfizer in a $43 billion deal. During an interview on the sidelines of this year’s American Society of Clinical Oncology annual meeting—where the Opdivo-Adcetris head-to-head data were presented—Seagen CEO David Epstein laid bare his longing for Pfizer’s ability to run several phase 3 trials for multiple drugs at the same time.

The strategy of combining an ADC with a PD-1 immunotherapy got a major boost recently from the combination of Seagen and Astellas’ Padcev and Merck’s Keytruda. In the EV-302 trial, the combo cut the risk of death by 53% compared with chemotherapy in previously untreated advanced bladder cancer.

Before that groundbreaking readout, thanks to a recent FDA accelerated approval in a subset of patients, Padcev already appeared on track to replace Adcetris as Seagen’s top-selling med. In the third quarter of 2023, Adcetris grew sales by 13% year over year to $246 million as Padcev’s sales jumped 89% to $200 million.