Two key advances in lung cancer treatment: maintenance therapy extends survival, while an ADC could replace some chemotherapy
Lung cancer experts invited by Goldman Sachs believe Amgen’s Imdelltra combination maintenance therapy could change the standard of care for small-cell lung cancer. An ADC combination from Merck and Kelun-Biotech also shows potential to replace chemotherapy, but global trials are still needed to confirm a survival benefit.
Original source：Goldman SachsFirst published on Unhidea：Original source date：
Key takeaway
Lung cancer treatment is moving toward more effective maintenance regimens and alternatives to chemotherapy, while competition among bispecific antibodies and the clinical role of new therapies remain dependent on global trial results and the pace of development.
Why could maintenance therapy change the standard of care for small-cell lung cancer?
Lung cancer experts invited by Goldman Sachs regard the phase III DeLLphi-305 trial of Amgen’s Imdelltra combined with Imfinzi as the result most likely to change clinical practice at this year’s ESMO meeting. After patients with extensive-stage small-cell lung cancer completed induction therapy with a platinum drug and etoposide, median overall survival was 21.1 months with the combination and 12.7 months with Imfinzi alone; the hazard ratio for death was 0.42.
Median progression-free survival was 7.4 months with the combination and 1.9 months in the control group. The experts expect the combination to become the standard maintenance regimen after regulatory approval.
However, approximately 10%–20% of patients experience rapid progression or a decline in physical condition during induction and cannot proceed to maintenance therapy. Moving these T-cell-engaging drugs into the induction phase therefore remains clinically meaningful, and the relevant phase III trials will take time to mature.
What are the opportunities and limitations of replacing chemotherapy with an ADC?
In first-line treatment of PD-L1-negative non-squamous non-small-cell lung cancer, median progression-free survival was 15.0 months with Merck and Kelun-Biotech’s sac-TMT plus Keytruda, versus 5.7 months with Keytruda plus chemotherapy in the control group. The hazard ratio for progression or death was 0.49; the interim overall survival hazard ratio was 0.58.
The experts believe that if a global study confirms a statistically significant overall survival benefit, replacing platinum and pemetrexed chemotherapy with sac-TMT could change standard treatment for this population.
The two regimens have different toxicity profiles: the incidence of severe anemia was 6.1% in the sac-TMT group and 20.4% in the chemotherapy group. However, the experts noted that ADC-related stomatitis can persist for months. Patients in Chinese trials are generally younger, while Western patients in global trials tend to be older and have more comorbidities; comparisons of tolerability must account for these population differences.
Why does competition among bispecific antibodies depend on the pace of global trials?
The experts see no clear biological difference in efficacy between BioNTech and Bristol Myers Squibb’s pumitamig and Summit Therapeutics and Akeso’s ivonescimab. BioNTech currently has more robust global clinical data from outside China, and long-term commercial differentiation may depend on the speed at which the two sides deploy global phase III trials across cancer types.
For the squamous non-small-cell lung cancer cohort of Summit’s HARMONi-3 trial, the experts consider a positive result highly likely, taking into account data from Akeso’s HARMONi-6 trial in China. They believe a progression-free survival hazard ratio below 0.65 would point more confidently to a statistically significant overall survival benefit; a ratio above 0.65 could also achieve that result.
How do the prospects differ for other lung cancer programs?
The experts are optimistic about the phase III trial of Moderna and Merck’s personalized cancer vaccine intismeran in resectable non-small-cell lung cancer, estimating the probability of success at approximately 70%–75%. Their rationale is that the mRNA platform may produce a more durable neoantigen-specific T-cell response than historical peptide vaccines.
The experts are more cautious about AstraZeneca and Daiichi Sankyo’s AVANZAR trial, estimating the chance of success in the TROP2-QCS biomarker-positive subgroup at roughly even odds, partly because the biomarker was identified through a retrospective analysis. They believe an overall survival hazard ratio of 0.75 or lower, with statistical significance, would favor clinical adoption.
The experts also believe Roche’s Krascendo 1 trial of divarasib has shown an overall survival benefit in KRAS G12C-mutated non-small-cell lung cancer and that the drug could become a new standard of care after approval.
