The BioPharm Brief: Two Phase 3 ADC Wins and a TCR Bispecific in PRAME-High Tumors

Welcome to The BioPharm Brief, your daily snapshot of developments shaping the biopharmaceutical industry. Welcome to The BioPharm Brief, your daily snapshot of developments shaping the biopharmaceutical industry. Today, two antibody-drug conjugates deliver phase 3 wins in hard-to-treat cancers, and a T-cell receptor-based bispecific shows durable responses in melanoma.

First, Bristol Myers Squibb and SystImmune reported that izalontamab brengitecan, or iza-bren, nearly doubled progression-free survival in EGFR-mutated non-small cell lung cancer. Iza-bren is a bispecific ADC that targets both EGFR and HER3. In the phase 3 PANKU-Lung01 trial, patients whose disease had progressed after EGFR tyrosine kinase inhibitor therapy lived a median of 11.1 months without progression on iza-bren, compared with 5.7 months on platinum-based chemotherapy. Response rates were 60.2% vs 34.5%, and interstitial lung disease occurred in fewer than 1% of patients. Overall survival data are still immature, and the trial was conducted in mainland China. The drug holds FDA breakthrough therapy designation in this setting.

Next, GSK and Hansoh reported phase 3 results for risvutatug rezetecan, or Ris-Rez, a B7-H3-targeted ADC in relapsed osteosarcoma, a bone cancer that mainly affects children and young adults. In the ARTEMIS-011 trial in China, patients who had already received at least 2 prior therapies lived a median of 5.5 months without progression on Ris-Rez, compared with 1.4 months on chemotherapy, a 67% reduction in the risk of progression or death. Serious treatment-related side effects were common, occurring in 93% of patients on Ris-Rez vs 83% on chemotherapy. Hansoh plans to file in China, while GSK continues a global sarcoma trial.

And Immatics presented phase 1b data for IMA402, a T-cell receptor-based bispecific that targets the cancer antigen PRAME. Because PRAME sits inside cancer cells, conventional antibodies can’t reach it. IMA402 instead recognizes PRAME fragments displayed on the cell surface and recruits T cells to attack. In patients with high PRAME expression, 32% had a confirmed response. In PRAME-high melanoma, responses lasted a median of 12.5 months, and 91% of patients treated in the recommended dose range were alive at one year. Side effects were mostly transient and low grade, though the data are preliminary and come from an uncontrolled study.

That’s today’s BioPharm Brief. For analysis and expert insights, please visit BioPharmInternational.com.

Key takeaways

• Iza-bren: The EGFR×HER3 bispecific ADC nearly doubled progression-free survival over chemotherapy in EGFR-mutated NSCLC after TKI failure.
• Ris-Rez: The B7-H3 ADC cut the risk of progression or death by 67% in relapsed osteosarcoma, but with frequent serious side effects.
• IMA402: The PRAME-targeted TCR bispecific produced durable responses in PRAME-high melanoma, with 91% one-year survival at the recommended dose.