The World Congress on Lung Cancer (WCLC) in Barcelona, Spain, showcased some of the most-anticipated clinical development candidates, with some impressive data intertwined with disappointing results.
AZ lifted by FLAURA 2 data
Among the highlights of WCLC are final overall survival (OS) data from AstraZeneca’s FLAURA 2 study of EGFR inhibitor Tagrisso (osimertinib) given in combination with chemotherapy as a first-line option for EGFR-mutated non-small cell lung cancer (NSCLC), showing a 23% reduction in the risk of death compared to Tagrisso alone.
Median OS for the combination came in at nearly four years (47.5 months), versus 37.6 months with Tagrisso monotherapy, and the survival rate at three years for the two groups was 63.1% and 50.9%, respectively.
The dual regimen is already approved in this setting, but the new OS results will help AZ face down a major challenge in first-line EGFR-mutated NSCLC treatment from Johnson & Johnson’s combination of Rybrevant (amivantamab) and Lazcluze (lazertinib).
Rybrevant/Lazcluze was cleared by the FDA as a first-line treatment for EGFR-mutated NSCLC last year, and uptake by oncologists has been strong on the back of data from the MARIPOSA trial, which showed that the regimen lowered the risk of death by 25% compared to Tagrisso after a little over three years’ follow-up.
Doubts linger about ivonescimab in HARMONi
Summit Therapeutics had already revealed in May that the HARMONi trial of its Akeso-partnered PD-1xVEGF bispecific ivonescimab plus chemo had failed to show a statistically significant improvement in OS compared to chemo alone, and the full data at WCLC did not restore confidence in the programme.
While it has been billed as a drug that could potentially outperform MSD’s mega-blockbuster Keytruda (pembrolizumab) in NSCLC, latterly clinical results have chipped away at that assessment. The latest progression-free survival (PFS) data from HARMONi falls into that category, with a divergence in efficacy between Asian and Western patients in the study raising alarm bells even though the overall result was positive.
Specifically, while the risk of death or disease progression was reduced 48% overall, the PFS difference was 45% for Asian patients but just 33% for those in North America or Europe. That adds to the OS miss, which has sparked speculation that Summit may not be able to file ivonescimab in the US based on its current data, although the company said it thinks that will be possible.
At WCLC, it was revealed that median OS after 2.5 years’ follow-up was 16.8 months with ivonescimab plus chemo and 14 months for chemo on its own, a 21% improvement, and the company is hoping that difference will, in time, cross the threshold for statistical significance.
MSD, Daiichi alliance bears fruit
There was good news for MSD and its partner Daiichi Sankyo in the antibody-drug conjugate (ADC) arena, after their B7-H3-directed candidate ifinatamab deruxtecan (I-DXd) hit the mark in a phase 2 trial involving patients with previously treated, extensive-stage small-cell lung cancer (ES-SCLC).
MSD – known as Merck & Co in the US and Canada – licensed rights to the ADC from Daiichi Sankyo in 2023 as one of three candidates covered by a deal that included an upfront payment of $4 billion.
Updated results from the IDeate-Lung01 study reported at WCLC revealed an objective response rate (ORR) of 48.2% among 137 patients in the study, including three complete responses, 63 partial responses, and 54 cases of disease stabilisation.
When looking specifically at the use of I-DXd as second-line treatment, the ORR rose to 56.3%, while for third-line it was 45.7%, which MSD said was an impressive result given the poor prognosis for ES-SCLC patients if their disease progresses despite platinum-based chemotherapy. The ADC has been granted breakthrough status from the FDA for the relapse/refractory ES-SCLC indication.
BMS’ ADC iza-bren adds HER3 activity to EGFR
Bristol Myers Squibb and Systimmune presented data at WCLC from a study of their potentially first-in-class EGFR and HER3-targeting ADC izalontamab brengitecan (iza-bren) as a first-line treatment for EGFR-mutated NSCLC in combination with Tagrisso.
Among 40 patients treated at the best-performing dose (2.5 mg/kg), iza-bren achieved an ORR of 100% and a confirmed ORR (cORR) of 95.0%, with two partial responses pending confirmation, a result described as “transformative” by investigator Dr Fei Zhou of Shanghai East Hospital.
Iza-bren is also being tested as a second-line monotherapy in EGFR-mutated NSCLC – new data at WCLC revealed a 56$ ORR in that setting – and it has been granted breakthrough status from the FDA for that use. It has moved into a phase 3 trial in China as a combination therapy.
Photo by National Cancer Institute on Unsplash
