Summit Therapeutics’ drug ivonescimab reduced the risk of lung cancer progression or death by nearly half compared to MSD’s blockbuster drug Keytruda (pembrolizumab) in Phase III data showcased on 8 September.
At the World Conference on Lung Cancer (WCLC) in San Diego, data revealed that Summit’s drug extended the time patients did not have tumour progression to a just over a median of 11 months, compared to nearly six months for patients treated with Keytruda. The 5.3-month difference in progression-free survival (PFS) translated into a statistically significant 49% reduction in the risk of cancer progression or death.
The Phase III study, known as HARMONi-2 (NCT05499390), involved 398 patients in China with PD-L1-positive, advanced non-small cell lung cancer (NSCLC). Patients were randomised to receive either ivonescimab – a bispecific antibody targeting PD-1 and VEGF – or Keytruda as the first treatment after diagnosis.
Summit had previously said the HARMONi-2 trial had met its primary endpoint in May 2024. The claim, which saw the small biotech’s stock price soar, has now been backed up with detailed data. Summit’s market cap is now $13.55bn.
This landmark study is especially noteworthy because, to date, no other Phase III clinical trials in NSCLC have shown such a statistically significant improvement in PFS in a direct comparison with Keytruda.
Keytruda, a PD-1 checkpoint inhibitor, generated $25bn last year, as per MSD’s financials. This revenue flow is expected to continue growing with GlobalData predicting that the blockbuster will pull in $33.7bn in 2028, when key Keytruda patents are set to expire.
Summit acquired ivonescimab in December 2022 after paying $500m to the China-based pharma company Akeso for commercial rights to ivonescimab in territories including the US and Europe. If approved, ivonescimab could generate up to $1.7bn in sales in 2030, as per GlobalData analysis.
GlobalData is the parent company of Pharmaceutical Technology.
Despite the excitement, the study did report a higher rate of severe side effects for ivonescimab compared to Keytruda. Among patients who took Summit’s drug, 29.4% experienced treatment-related adverse events (TRAEs) that were grade 3 or above, compared with 15.6% of patients taking Keytruda. These TRAEs included abnormal amounts of protein in the urine, and other abnormalities detected in laboratory tests.
Based on the results of HARMONi-2, Summit announced its plans to initiate the Phase III HARMONi-7 trial in early 2025. The study aims to compare ivonescimab monotherapy to Keytruda monotherapy in patients with metastatic NSCLC whose tumours have high PD-L1 expression.
In the announcement accompanying the results, Summit’s CEO Robert Duggan said: “This is a historic moment for ivonescimab, Team Summit, our partners at Akeso, and most importantly, we believe this is the beginning of a landscape shift for treatment options for patients living with cancer.”
