Summit Therapeutics and Akeso’s closely watched dual-acting lung cancer drug ivonescimab combined with chemotherapy significantly delayed disease progression when compared to the immunotherapy Tevimbra and chemo, according to results of a trial in Chinese patients, the companies released Sunday.
The data only deepens the controversy over ivonescimab, which has drawn close attention since early data emerged last year suggesting it outperformed Merck & Co.’s immunotherapy Keytruda in a non-small cell lung cancer trial. Subsequent data have shown a less-decisive benefit, although ivonescimab’s progress to date has sparked heavy investment in its drug class, which simultaneously blocks the immune checkpoint PD-1 and the blood vessel-building protein VEGF.
The most recent data, presented at the European Society for Medical Oncology meeting in Berlin, came from a Phase 3 trial called HARMONi-6 run by China-based developer Akeso. The trial tested an ivonescimab-chemo combination in newly diagnosed patients with advanced lung cancer or disease that has spread outside the lungs. In this setting, people would likely receive chemo with a PD-1 inhibitor, often Keytruda.
In designing the trial, Akeso chose as its comparative PD-1 BeOne Medicines’ Tevimbra, which has been approved for lung cancer in China but not in the U.S. The trial found the ivonescimab combination reduced the risk of progression by 40% compared to the Tevimbra-based one, helping people who got ivonescimab live a median of 11 months before progressing compared to seven months for those who got Tevimbra.
The benefit was seen regardless of whether people tested positive for the PD-L1 protein that ivonescimab and Tevimbra target.
The two regimens had a similar side effect profile. Trial enrollees who got ivonescimab had a higher incidence of certain severe side effects related to VEGF-targeting treatment, such as hypertension or kidney damage markers.
Some Wall Street analysts saw the data as exceeding expectations, especially since ivonescimab showed a statistically significant benefit at an early data check.
Furthermore, it is a sign that a large global trial called HARMONi-3, comparing ivonescimab and chemo with Keytruda-chemo, will be positive for ivonescimab, some analysts wrote.
Others were more skeptical, pointing to a shrinking difference in progression-free survival past the median checkpoint that might mean ivonescimab won’t help people live longer overall, as well as declining response benefit. “We're not convinced monotherapy/chemo combo datasets will show a practice changing benefit” on patient survival, wrote Jefferies analyst Akash Tewari.
Summit shares fell 5% in Monday morning trading. The company also just released its third quarter results, in which it reported spending $173 million so far this year, reducing its cash holdings to $239 million as of Sept. 30. Without a bigger development partner, Summit may need to raise more money, wrote Leerink Partners analyst Daina Graybosch.
