Tambotatug pelitecan (Tam-Peli), a novel B7-H3–targeting antibody–drug conjugate (ADC), delivers significant survival boost in relapsed small-cell lung cancer (SCLC) as compared with topotecan, according to the phase III TAISHAN-302 trial.
TAISHAN-302 met its primary endpoint, with Tam-Peli demonstrating a significant and clinically meaningful improvement in overall survival (OS) compared with topotecan, reported principal investigator Prof Li Zhang from Sun Yat-sen University Cancer Center in Guangzhou, Guangdong Province, China, during his presentation at the annual WCLC congress.
Median OS was 13.3 months with Tam-Peli vs 9.4 months with topotecan, representing a 54-percent reduction in the risk of death (hazard ratio [HR], 0.46, 95 percent confidence interval [CI], 0.35–0.62; p<0.0001). The median follow-up was 9.2 months in the Tam-Peli group and 9.5 months in the topotecan group. [N Engl J Med 2026;doi:10.1056/NEJMoa2610229]
“The OS benefit with Tam-Peli was consistent across all subgroups,” including those defined by smoking history, prior PD-(L)1 therapy, the presence of brain or liver metastases, disease stage at enrolment, and B7-H3 expression level, Zhang noted.
Compared with topotecan, Tam-Peli also yielded marked improvements in progression-free survival (PFS) and objective response rate. Median PFS was 7.4 vs 2.8 months, with a 71-percent reduction in the risk of disease progression or death (HR, 0.29, 95 percent CI, 0.23–0.37; p<0.001). Significantly more patients in the Tam-Peli group achieved objective response, as confirmed by investigator assessment according to RECIST, at 59.1 percent vs only 9.7 percent in the topotecan group (p<0.001).
Intracranial efficacy demonstrated
In a subset of patients with brain metastases at baseline, Tam-Peli showed significant intracranial activity, according to Zhang.
Median intracranial PFS was 6.1 months with Tam-Peli vs 4.2 months with topotecan (HR, 0.43, 95 percent CI, 0.27–5.6; p=0.0002). Investigator-assessed intracranial objective response rate was 32.4 percent vs 2.9 percent (p<0.0001), and intracranial disease control rate was 90.5 percent vs 59.4 percent (p<0.0001), respectively.
Low rates of high-grade AEs
Importantly, “the survival benefit from Tam-Peli was achieved without an increase in the risk of high-grade adverse events (AEs),” Zhang said.
While treatment period longer with Tam-Peli vs topotecan (median, 31.1 vs 10.1 weeks), grade ≥3 treatment-related AEs (TRAEs) and serious TRAEs occurred less frequently in the Tam-Peli group (46.4 percent vs 74.7 percent and 25.9 percent vs 36.4 percent, respectively). TRAEs leading to dose reduction were also less common in the Tam-Peli vs the topotecan group (25.9 percent vs 36.9 percent).
The most common grade ≥3 AEs related to treatment with Tam-Peli were haematologic in nature, including neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anaemia.
“No treatment-related deaths were reported in the Tam-Peli group, and the incidences of all-grade TRAEs and dose interruption were similar between the treatment groups,” Zhang said.
Interstitial lung disease (ILD)/pneumonitis occurred in 4.9 percent of patients receiving Tam-Peli vs 1.4 percent of those receiving topotecan, including grade 3 events in 0.9 percent of patients in both groups. There were no grade 4 or 5 ILD events reported.
“The safety profile of Tam-Peli was generally favourable and manageable, with no new or unexpected safety signals identified,” Zhang said.
New standard emerging
“Results from TAISHAN-302 establish Tam-Peli as a potential new standard of care for relapsed SCLC,” Zhang said. “The drug provides an additional treatment option for patients with relapsed SCLC, for whom limited therapeutic options are available
He emphasized the need for treatment options with distinct mechanisms of action and complementary safety profiles, given that relapsed SCLC continues to be a highly aggressive disease.
“Topotecan has long served as the standard second-line therapy, but survival benefit remains modest,” Zhang noted. [J Clin Oncol 1999;17:658-667; J Clin Oncol 2014;32:4012-4019; J Clin Oncol 2024;42:2317-2326] “[Furthermore,] robust evidence of a favourable survival benefit from new treatment regimens is limited,” he added.
Zhang pointed out that the FDA-approved tarlatamab, a bifunctional T-cell engager that targets delta-like ligand 3 (DLL3) and CD3, provides the most relevant contemporary benchmark of efficacy. In the DeLLphi-304 trial, tarlatamab was associated with median overall survival of 13.6 months, which was higher than the 8.3 months with chemotherapy. Adverse events consisted mainly of cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome. [N Engl J Med 2025;393:349-361]
“Tam-Peli showed a similar survival benefit in our phase III trial, with a median OS of 13.3 months,” he said. However, Zhang acknowledged that cross-trial comparisons require cautious interpretation, because the trials differed with respect to the demographic characteristics of the patients, the dose used in the control group, and the use of subsequent therapy.
“For instance, our trial involved a relatively high percentage of patients who were nonsmokers and a high percentage of male patients, characteristics that were consistent with those of the patient populations in other trials conducted in China,” Zhang said.
“Furthermore, Tam-Peli is an antibody–drug conjugate that represents a new therapeutic approach: the mechanism of action is distinct from that of tarlatamab, and the safety profile is different. As such, Tam-Peli provides an additional treatment option for patients with relapsed SCLC, for whom limited therapeutic options are available,” he continued.
Rapidly changing treatment landscape
“This is a really exciting time for SCLC, with new treatments rapidly emerging and changing the landscape overnight,” said study discussant Prof Anne Chiang from the Yale School of Medicine in New Haven, Connecticut, US.
ADCs, including Tam-Peli, represent “great options for our patients,” Chiang added. “I think we’re going to have to turn to ADC biology to understand some of the nuances to differentiate between agents.”
Chiang pointed out that clinicians have to think about premature payload release in the circulation and how that affects toxicity, how well ADCs penetrate into the tumour, target recognition and what levels of targets or their spatial distribution, among others.
“Finally, resistance is going to be really important to understand in order to know how to sequence these agents… Resistance to different chemotherapies favours the idea of sequencing therapies, perhaps with different mechanisms of action, and also creates opportunities for combining these agents with other agents that perhaps target resistance mechanisms,” she said.
Chiang predicted that in 2 to 5 years, ADCs would become the new second-line treatment for relapsed SCLC and could even replace chemotherapy in the frontline setting. She hoped for an end to the era of one-size-fits-all treatment for SCLC, saying, “We need to make way for sequencing therapies guided by tumour surface proteins and biologically distinct SCLC subtypes.”
TAISHAN-302
TAISHAN-302 included 451 SCLC patients (median age 62 years, 82.9 percent male, 71 percent current of former smokers) who progressed after one prior line of platinum-based therapy, had at least one measurable lesion, and had an ECOG performance score of 0-1. Those with stable asymptomatic brain metastases were eligible.
The patients were randomly assigned to receive intravenous treatment with Tam-Peli (n=225) or topotecan (n=226). Tam-Peli was administered at a dose of 2 mg/kg on day 1 of each 3-week cycle (with a maximum dose of 200 mg per cycle), while topotecan was administered at a dose of 1.2 mg per m2 of body-surface area on days 1 through 5 of each 3-week cycle according to the approved prescribing information in China. Treatment was continued until disease progression, the development of unacceptable side effects, initiation of new anticancer therapy, withdrawal of consent, loss to follow-up, death, loss of clinical benefits as assessed by the investigators,
Of the patients, 434 (96.2 percent) had systemic disease, 155 (34.4 percent) had a history or presence of brain metastases at baseline, 393 (87.1 percent) had received previous anti–PD-L1 or anti–PD-1 therapy, and 220 (48.8 percent) had platinum-resistant disease, as defined by disease progression after a chemotherapy-free interval of less than 90 days.