WCLC: Lung cancer news from BioNTech, Akeso, and Roche
Aakash Dhage
As the World Conference on Lung Cancer (WCLC) draws to a close, here is some of the late-breaking clinical trial data that made waves at the congress.
BioNTech reports survival data with CTLA-4 shot
BioNTech and partner OncoC4's anti-CTLA-4 immunotherapy gotistobart almost doubled survival in a trial involving patients with a hard-to-treat form of lung cancer, ahead of a pivotal readout due next year.
The results come from the first stage of the PRESERVE-003 phase 3 trial, which is testing gotistobart (formerly ONC-392) in patients with advanced, squamous non-small cell lung cancer (NSCLC) whose disease has progressed despite prior immunotherapy and chemotherapy.
Median overall survival (OS) in this group of lung cancer patients is typically less than a year, but PRESERVE-003 showed that patients treated with gotistobart had a median OS of 18.5 months, compared to 10 months in the comparator group that received docetaxel chemotherapy. The objective response rate was 20% with gotistobart versus 4.8% with docetaxel. The study will now progress to stage 2, with the most effective dose of the anti-CTLA-4 drug taken forward.
BioNTech paid $200 million upfront to license gotistobart in 2023, gaining the right to co-develop the drug as a monotherapy and in combination with PD-1/PD-L1 inhibitors.
The drug is designed to offer the efficacy in depleting regulatory T-cells (Tregs) seen with other CTLA-4 inhibitors, like Bristol Myers Squibb's Yervoy (ipilimumab) and AstraZeneca's Imjudo (tremelimumab), but reduce the side effects seen with these first-generation antibodies.
Tolerability remained an issue with gotistobart in PRESERVE-003, notably colitis and liver enzyme elevations, with treatment discontinuations due to side effects occurring in 15.6% of patients versus 4.9% for docetaxel.
Summit, Akeso's ivonescimab extends survival in frontline NSCLC
New data from the HARMONi-2 trial of Akeso and Summit Therapeutics' PD-1xVEGF bispecific antibody ivonescimab showed a significant increase in survival when used as first-line treatment for patients with PD-L1-positive, locally advanced or metastatic NSCLC, compared to MSD's PD-1 inhibitor Keytruda (pembrolizumab).
After 36 months of follow-up, median OS was 30.8 months with ivonescimab, versus 22.6 months with Keytruda, which equates to a 27% reduction in the risk of death. Furthermore, the survival rate at the three-year timepoint in the Chinese study was 35% with Akeso and Summit's drug and 33.1% in the control arm.
Ivonescimab received regulatory approval in China for this patient population in April 2025. Summit, which has rights to the drug outside Greater China, is running an international pivotal trial (HARMONi-7) in patients with PD-L1 high-expressing NSCLC, with results due in 2028. It is also running HARMNONi-3, which combines ivonescimab with chemo in the first-line setting and more accurately reflects current clinical practice in frontline NSCLC treatment. Initial data from that study is due later this year.
HARMONi-2 is the first randomised phase 3 study to demonstrate a statistically significant OS benefit over Keytruda monotherapy in this patient population, raising the prospect that drugs targeting both PD-1/PD-L1 and VEGF – of which there are many in clinical development – could provide a step up in efficacy in NSCLC.
Roche, MediLink ADC shows promise in SCLC
Roche's B7-H3-directed antibody-drug conjugate tambotatug pelitecan (tam-peli) – licensed from China's MediLink earlier this year for $570 million upfront – delivered in a major phase 3 readout, the TAISHAN-302 study comparing the drug to topotecan in relapsed small-cell lung cancer (SCLC).
Tam-peli reduced the risk of death by 54% versus chemo in the 451-patient Chinese study, with median OS of 13.3 months and 9.4 months, respectively, and progression-free survival (PFS) coming in at 7.4 versus 2.8 months.
The positive result is the second for a B7-H3-targeting ADC in relapsed SCLC at this year's WCLC, coming alongside GSK's reveal of Chinese data with risvutatug rezetecan (ris-rez), licensed from Hansoh Pharma for $185 million upfront in 2023. GSK has already started a phase 3 programme aimed at bringing ris-rez to international markets, while Roche said it is planning to "rapidly initiate" global studies of the drug.
Both ADCs are a little behind the leader in the category, Daiichi Sankyo and MSD's ifinatamab deruxtecan, which is already under FDA review for extensive-stage SCLC, with a decision due next month.
Photo by Aakash Dhage on Unsplash
