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#ESMO24 roundup: New data on Amgen’s PRMT5 inhibitor seem lackluster, and Jazz’s HER2 antibody

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On Sunday evening, abstracts from the European Society for Medical Oncology were released. While some of oncology’s most exciting recent data were reported a week before at a separate conference, ESMO still has late-breaking results to come, in addition to three key biotech readouts from the first wave of abstracts.

Endpoints News will have four people on the ground covering ESMO, so stay tuned for our coverage of the cancer conference and register for our virtual event, where we will be speaking to Daiichi Sankyo’s CEO Ken Keller and Novartis radiopharma leader Jeevan Virk.

For Amgen’s PRMT5 inhibitor, it’s round two versus BMS/Mirati: In Amgen’s exploratory study of patients with solid tumors, two of 11 patients saw their tumors shrink at least 30% in non-small cell lung cancer, two of 11 with bile duct cancer responded, and two of 16 with pancreatic cancer had a response.

That means that across the three cancer types, response rates were all below 20%. That’s down from what Amgen previously reported in 2023 when 28% (5/18) of patients responded to treatment. (The company has said there is one additional unconfirmed response each in non-small cell lung cancer and pancreatic cancer, and updated results are expected during an ESMO presentation next Monday.)

PRMT5 inhibitors target a key driver behind roughly 10-15% of all cancers, and because of that have been of great interest to drug developers. Bristol Myers Squibb’s MRTX1719 (acquired with its $4.9 billion purchase of Mirati Therapeutics) resulted in six responses in 18 patients who received a range of doses, according to data published last year. Tango Therapeutics is also developing a PRMT5 inhibitor.

In Amgen’s study, patients were given either 800 mg or 1200 mg (the maximum tolerated dose) once a week. The median duration of response was 8.3 months.

Two of 18 patients who were in the 1200 mg cohort in the dose escalation portion of the study experienced dose-limiting toxicities, including grade 3 vomiting and grade 3 hypokalemia, or low potassium. The most common treatment-related adverse events were nausea, fatigue, vomiting and decreased appetite, according to the abstract.

Jazz’s HER2 antibody shows promise in Phase 2: The company’s drug zanidatamab added to chemotherapy achieved an 84% overall response rate in 37 evaluable patients with advanced or metastatic gastroesophageal adenocarcinoma (GEA). Four patients had a complete response. The data represent a “slight improvement” from the 79% ORR reported in a previous readout last year, according to Leerink analysts.

The evaluable patients were also free from disease progression for a median of 15.2 months at an average follow up of 41.5 months. Overall survival data, meanwhile, were still maturing at the Jan. 17 cutoff date. On safety, eight patients had serious side effects, and there were no deaths related to treatment.

A combination of zanidatamab plus chemotherapy and BeiGene’s tislelizumab is being tested in the Phase 3 HERIZON-GEA-01 trial in people with first-line GEA, with a topline readout expected next year.

Bicycle Therapeutics also reported updated results on its bladder cancer drug, where it hopes to match Pfizer’s Padcev on efficacy and win on safety. Read our coverage here.


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