Immutep believes its LAG-3 candidate eftilagimod alpha may have a path to approval in first-line head and neck cancer after reporting what one analyst deems “impressive” overall survival data.
Monday, Immutep said a combination of eftilagimod and Merck & Co.’s Keytruda helped patients live a median of 17.6 months when used as first-line therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with PD-L1 expression below a combined positive score (CPS) of 1.
The overall survival result came from 31 evaluable patients enrolled in cohort B of a phase 2b trial coded Keynote-C34, or Tacti-003. The trial doesn’t have an active internal control arm. But as Immutep noted, the 17.6-month median looks better than historical data from two existing standard-of-care regimens. In a note, Jefferies analyst David Stanton, M.D., called the survival readout “impressive.”
Immutep suggests that a high unmet need for first-line treatment of PD-L1-negative HNSCC could potentially pave eftilagimod a path to approval, and the Australian biotech has requested a meeting with the FDA to discuss that. Eftilagimod already boasts an FDA “fast track” designation in first-line HNSCC.
“Given the strength of the efficacy and safety results generated to date with efti in combination with [Keytruda], we will meet with regulators to discuss next steps and potential paths to approval,” Immutep CEO Marc Voigt said in a statement.
According to Voigt, the eftilagimod-Keytruda combo’s value proposition lies in that it offers a potential immunotherapy-only regimen, while the standards today for PD-L1-negative patients all include chemotherapy. Eftilagimod is a LAG-3 fusion protein, which activates antigen-presenting cells to boost an immune response, according to Immutep.
Back in 2019, the FDA approved Keytruda in combination with chemotherapy for all patients with first-line HNSCC, including those with PD-L1-negative tumors. The approval was based on the phase 3 Keynote-048 trial showing that Keytruda plus chemo reduced the risk of death by 23% versus Eli Lilly’s EGFR inhibitor Erbitux and chemo in the overall population regardless of PD-L1 expression levels. At the time, the FDA simultaneously approved Keytruda monotherapy but only for PD-L1-positive tumors that express the biomarker at CPS score at or above 1.
A post hoc analysis of Keynote-048 later showed that Keytruda-chemo didn’t demonstrate a clear overall survival benefit over Erbitux-chemo in the PD-L1-negative subgroup. The median overall survival was 11.3 months versus 10.7 months. The death risk was even 21% higher for that subgroup for the Keytruda-chemo arm, although researchers cautioned that this analysis was only descriptive and limited by the small number of patients involved.
Regardless of Keytruda-chemo’s position, eftilagimod and Keytruda’s 17.6-month median overall survival length now looks better than those by the two chemo-containing regimens with the obvious caveat of a cross-trial comparison.
The latest overall survival showing builds on some promising tumor response data from the Immutep regimen. Last year, Immutep reported a 35.5% objective response rate—including 12.9% complete responses—for eftilagimod and Keytruda from cohort B of Tacti-003. The numbers compare favorably to Keytruda-chemo’s 30.8% ORR—including 2.6% CR—in Keynote-048’s PD-L1-negative subgroup.
“Driving durable responses that translate into clinically meaningful survival holds tremendous promise for these patients in need of more tolerable and efficacious therapies,” Voigt said in a statement Monday.
Immutep looks poised to carve out a niche market from PD-L1-negative disease, which makes up about 20% of first-line HNSCC patients, according to the company. As Voigt noted, there’s a lack of competitor chemo-free trials targeting this population.
Merck recently partnered with Exelixis to combine Keytruda with the latter company’s investigational tyrosine kinase inhibitor zanzalintinib in HNSCC. However, the pair’s phase 3 Stellar-305 trial is only testing that combo in PD-L1-positive patients.
Similarly, Merus, with an FDA “breakthrough therapy” designation, is evaluating its EGFRxLGR5 bispecific antibody petosemtamab with Keytruda in first-line HNSCC in the phase 3 LiGeR-HN1 trial—again only in PD-L1-positive patients.