ASCO: Regeneron's Opdualag rival records double the historical response rate in melanoma

Regeneron believes its LAG-3 inhibitor and PD-1 inhibitor combo for patients with advanced melanoma could serve as a rival to Bristol Myer Squibb’s Opdualag, although a significant portion of patients discontinued treatment in a phase 1 study.

“The next big kid on the block is LAG-3,” Israel Lowy, M.D., Ph.D., Regeneron’s SVP of clinical sciences and head of translational science and oncology, told Fierce Biotech in an interview ahead of this year’s American Society of Clinical Oncology annual meeting, where the company will present data from a phase 1 study of fianlimab in 98 patients with advanced melanoma. 

The Regeneron team will show that fianlimab—an investigational monoclonal antibody that targets immune checkpoint receptor LAG-3 on T cells—in combination with Libtayo had an objective response rate (ORR) of 61% across three cohorts. That rate is almost double what has historically been seen with anti-PD-1 used as a monotherapy, Regeneron said in a Thursday afternoon press release

For the phase 1 trial, three separate groups of adults with unresectable or metastatic melanoma received 1,600 mg of fianlimab and 350 mg of Libtayo for 12 months, with tumor measurements taken every six weeks for six months, and then every nine weeks after that. The median treatment duration was 32.9 weeks. The phase 1 study has 25 primary endpoints and an estimated total enrollment of 333 patients.


The first cohort consisted of 40 patients with first-line or second-line advanced melanoma who had never received anti-PD(L)1 treatment before. The data show a 63% overall response rate, with 15% (6) of patients having a complete response and 48% (19) of patients experiencing a partial response. Thirty patients (75%) in the group discontinued treatment.

Regeneron’s Lowy, who is also listed as an author on the new data abstract, said the research team was “shocked” when they saw the initial ORR for the first cohort, so they repeated the study again in two more cohorts.

The second cohort was made up of 40 first-line advanced melanoma patients who had never received an anti-PD(L)1 before. The data show a 63% ORR, with 13% (5) of patients experiencing a complete response and 50% (20) of patients with a partial response. Twenty-one patients (52%) discontinued treatment.

The third group was 18 patients with first-line advanced melanoma that had prior (neo)adjuvant systemic therapy, including 13 patients who had previously received anti-PD-1 treatment. The cohort had a 56% ORR, with 6% (1) patient having a complete response and 50% (9) partial responses. Twelve patients (66%) discontinued treatment. 

“We're really not that far behind the market leader, which is BMS,” Lowy said. “What we are most excited about with what we're bringing forward is that we think we have differentiated efficacy.”

Overall, Regeneron’s combo showed a 61% ORR at a median 12.6 month follow-up among 98 patients. This compares to a 43% ORR among 355 patients who received BMS’s rival anti-PD1 and LAG-3 blocking antibody combo, dubbed Opdualag, at 19.3 months. The combination gained FDA approval in March 2022—the first LAG-3-blocking antibody for patients with unresectable or metastatic melanoma.

Opdualag had a median progression-free survival (PFS) of 10.1 months in a phase 2/3 trial in patients with previously untreated metastatic or unresectable melanoma, according to a company release. In comparison, Regeneron’s first cohort had a PFS of 24 months, while cohort two had a PFS of 14 months and cohort three had a PFS of 12 months.  

“So, you may ask, why is our response rate better? And the answer is: I don't know,” Lowy said. “I will say that we've been able to give higher doses that BMS was able to give because BMS ran into toxicity types that we're not seeing so far.”

For BMS, grade 3 or 4 treatment-emergent adverse events (TEAEs) occurred in 18.9% of patients receiving Opdualag, with TEAEs leading to discontinuation for 14.6% of patients receiving the combo.   

Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 43.9% of patients receiving Regeneron’s combo, with 16.3% of participants discontinuing treatment because of a TEAE. Grade 3 events are severe but not immediately life-threatening, while grade 4 events are life-threatening and grade 5 events can be fatal.

Regeneron’s combo treatment had a similar safety profile to Libtayo as a monotherapy, according to Lowry, with the exception of adrenal insufficiency, a disorder that occurs when the adrenal glands don't produce a sufficient amount of certain hormones, such as cortisol. More than 12% of patients had adrenal insufficiency, with 4.1% of patients having a grade 3 or higher adverse event (AE) associated with it.  

Overall, 64% (63) of patients in the Regeneron trial discontinued treatment. The top cited reason for discontinuation was disease progression, reported by 52% (33) of patients who stopped treatment.

The median patient age was 68 and 89.8% of participants were white, which may be due to the nature of melanoma, a serious skin cancer that is more commonly reported in people with lighter skin.

Regeneron is currently running two phase 3 studies assessing the combo, one in advanced non-small cell lung cancer and one in adolescent and adult patients with previously untreated, unresectable, locally advanced or metastatic melanoma.

Editor's Note: This article was updated at 11 a.m. ET to exclude an inaccurate statement that said fianlimab isn't cataloged in Regeneron's current pipeline.