New ESMO oncology data: Imdelltra expands its potential, lung cancer competition becomes tougher
Bernstein believes Imdelltra’s first-line maintenance data could significantly expand its commercial opportunity; INT strengthens the outlook for postoperative adjuvant treatment, while new lung cancer combinations raise the competitive bar. But the commercial value of efficacy improvements must also be assessed against toxicity, treatment duration and the patient population.
Original source：BernsteinFirst published on Unhidea：Original source date：
Key takeaway
Bernstein is optimistic about several oncology advances, but their commercial impact depends on whether they can reach larger patient populations, extend treatment duration and offer a favorable efficacy–toxicity trade-off when replacing existing regimens.
Why could Imdelltra open up a larger market?
In DELLPHI-305, adding Imdelltra to durvalumab as first-line maintenance treatment for extensive-stage small cell lung cancer extended median overall survival from 12.7 months to 21.1 months, with a hazard ratio for death of 0.42.
Bernstein roughly estimates that its peak commercial potential could be about three times the current second-line opportunity: there are more first-line patients, and treatment continues until disease progression, resulting in longer use. But earlier use would also reduce the subsequent second-line treatment rate.
Why can the INT opportunity not be assessed solely against preoperative treatment?
In the first interim analysis of a phase III trial of Moderna’s INT plus Keytruda as postoperative adjuvant treatment for melanoma, the hazard ratio for recurrence-free survival was 0.58. Doctors estimate that only 15%–25% of nonmetastatic patients are eligible for preoperative treatment, while about 75% of early-stage patients are staged only after surgery, so the two approaches cover different populations.
Assuming broad access and a low adverse-event burden, Bernstein expects INT could increase Keytruda’s share of adjuvant treatment from about 50% and take share from Opdivo. The distant metastasis-free survival result was weaker than in phase II; this is associated with events occurring later and the inclusion of approximately 30% stage II patients, whose disease tends to recur more slowly, in phase III. The overall survival benefit has not yet reached statistical significance.
In a phase I pancreatic cancer study, 11 patients remained recurrence-free, with median follow-up of 17 months and a maximum of 22 months. The patients were highly heterogeneous; assessing whether INT can improve on existing efficacy requires observing durability beyond two years.
Padcev’s efficacy improves, so why might revenue per patient decline?
In VOLGA, which studied muscle-invasive bladder cancer patients ineligible for cisplatin, just three preoperative cycles of Padcev plus durvalumab produced hazard ratios of 0.51 for event-free survival and 0.58 for overall survival.
This strengthens Padcev’s position in curative treatment, but if doctors prefer this short course, drug use per patient will be lower than with the preoperative and postoperative regimen in KEYNOTE-905. The allocation of share between the two will depend on more mature efficacy data.
Why is Keytruda monotherapy becoming a harder comparator to justify?
PERSEE directly compared Keytruda plus chemotherapy with monotherapy in non-small cell lung cancer patients with high PD-L1 expression: median progression-free survival was 16.1 months versus 6.9 months; the overall survival difference did not reach statistical significance.
The cost of combination treatment is higher toxicity, with treatment-related serious adverse events occurring in 54% versus 19%; the choice must still be tailored to the individual. Bernstein therefore believes the competitive case for TROFUSE-007, which uses monotherapy as its control, is less compelling, and that patients suitable for combination treatment are better compared against Keytruda plus chemotherapy.
Where does Sac-TMT’s new advantage come from?
In OPTI-TROP-LUNG-06, conducted in China, patients with PD-L1 below 1% who received Sac-TMT plus Keytruda had median progression-free survival 2.6 times that of patients receiving Keytruda plus chemotherapy. The advantage came mainly from a longer duration of response of 13.6 months versus 6.8 months in the control group; objective response rates were similar, at 50.2% versus 47.3%.
Bernstein believes this raises the bar for other first-line ADCs and PD-1×VEGF regimens and supports Merck considering a broader first-line trial. Dose reductions in the combination improved adverse reactions, but toxicities such as fatigue were more persistent, and patient-reported outcomes will influence the choice of regimen.
Which drugs will next-generation KRAS therapies challenge first?
In KRASCENDO-1, median progression-free survival with Divarasib in second-line non-small cell lung cancer was 9.8 months, versus 5.7 months for the comparator, Krazati or Lumakras.
Bernstein notes that the two older drugs derive about half their revenue from this setting, and Divarasib will compete directly with them once approved; next-generation drugs are also advancing into first-line and adjuvant treatment, moving competition into earlier settings.
