Temab-A Shows Promising Survival in Pretreated Nonsquamous NSCLC

Telisotuzumab adizutecan (Temab-A), an investigational c-Met-directed antibody-drug conjugate (ADC), produced encouraging overall survival (OS) in heavily pretreated nonsquamous non-small cell lung cancer (NSCLC), particularly in epidermal growth factor receptor (EGFR) wild-type tumors with high c-Met expression, according to updated results from the first-in-human M21-404 study presented at the 2026 European Society for Medical Oncology Congress.¹

At the June 2, 2026, data cutoff, the EGFR wild-type cohort (n = 48) had a median follow-up of 30.1 months (range, 0.4-35.5). Median OS was 13.8 months (95% confidence interval [CI], 9.0-25.2), with 33 deaths (69%), and median progression-free survival (PFS) was 6.8 months (95% CI, 5.4-7.3), with 40 events (83%). The objective response rate (ORR) was 50% (24/48; 95% CI, 35.2-64.8), with a median duration of response (DOR) of 5.6 months (95% CI, 4.2-11.3).¹

Of 46 patients with immunohistochemistry results, 20 (43%) had c-Met 3+ staining in at least 10% of tumor cells. This group had an ORR of 60% (12/20), median PFS of 7.2 months, median OS of 25.2 months (95% CI, 7.5-not estimable [NE]), and median DOR of 5.6 months, vs 42% (11/26), 5.4 months, 9.7 months, and 5.4 months (95% CI, 2.7-NE) below that cutoff. Investigators proposed this as a potential selection threshold.¹

At the 2.4 mg/kg dose, EGFR wild-type patients had an ORR of 54% (21/39) and median PFS, OS, and DOR of 6.8, 14.7, and 5.7 months. In the 37% (14/38) with high c-Met, these were 64% (9/14), 7.6, 19.2 (95% CI, 7.3-NE), and 5.7 months, vs 46% (11/24), 5.4, 10.5, and 5.4 months below the cutoff.¹

In the EGFR-mutant cohort (n = 41; median follow-up, 29.5 months [range, 0.4-34.8]), median OS was 16.2 months (95% CI, 11.6-19.9), with 31 deaths (76%), and median PFS was 10.9 months (95% CI, 8.3-12.3), with 39 events (95%). The ORR was 63% (26/41; 95% CI, 46.9-77.9), with a median DOR of 9.7 months (95% CI, 8.3-13.5).¹

c-Met level showed little link to outcomes in this cohort. The 49% (19/39) with c-Met 3+ in at least 25% of cells had an ORR of 68% (13/19) and median PFS, OS, and DOR of 12.3, 16.2, and 10.9 months, vs 60% (12/20), 9.5, 16.2, and 9.0 months below the cutoff. At 2.4 mg/kg, the ORR was 61% (22/36), with median PFS, OS, and DOR of 10.9, 16.2, and 9.7 months; the 41% (14/34) with high c-Met had an ORR of 64% (9/14) and corresponding values of 12.3, 16.2 (95% CI, 9.6-NE), and 10.9 months. c-Met selection may not be needed here, the authors said.¹

“Temab-A exhibited promising efficacy in heavily pretreated patients with non-squamous NSCLC; OS rates compared favorably with those reported in the same indications with chemotherapy or other ADCs,” lead study author David Sommerhalder, MD, of NEXT Oncology, and colleagues concluded in the presentation.¹

Temab-A Safety Profile in Advanced NSCLC

Most treatment-related adverse events (TRAEs) were hematologic or gastrointestinal, with no new safety signals. Median treatment duration was 5.6 (range, 0.7-34.5) and 10.0 (range, 0.7-26.9) months in EGFR wild-type and EGFR-mutant patients.¹

Any-grade TRAEs occurred in 98% and 100% of these cohorts, respectively, and grade 3 or higher TRAEs in 50% and 63%. TRAEs led to discontinuation in 21% and 17%, dose interruption in 48% and 63%, and dose reduction in 40% and 49%. Treatment-related deaths occurred in 2 (4%) and 1 (2%) patients, all adjudicated as interstitial lung disease or pneumonitis.¹

M21-404 Phase 1 Trial Design

Temab-A links telisotuzumab, a c-Met antibody, to a topoisomerase 1 inhibitor payload. The study (NCT05029882) enrolled adult patients with an Eastern Cooperative Oncology Group performance status of 0 or 1, measurable disease per RECIST v1.1, and progression after platinum-based chemotherapy and immune checkpoint or targeted therapy.^1,2

Expansion cohorts included second-line or later EGFR wild-type nonsquamous disease (21 c-Met-selected and 27 unselected patients), third-line or later c-Met-unselected EGFR-mutant nonsquamous disease, and a squamous cohort (n = 40) not reported here. Most patients received 2.4 mg/kg (39 EGFR wild-type, 36 EGFR-mutant); the rest received 3.0 mg/kg. The primary end point was investigator-assessed confirmed ORR; DOR, PFS, and OS were secondary end points.¹

Median ages were 66 (range, 32-85) and 64 (range, 43-88) years, with a median of 2 (range, 1-9) and 3 (range, 1-8) prior therapy lines in the EGFR wild-type and EGFR-mutant cohorts. Among EGFR wild-type patients, 96% had received a checkpoint inhibitor and 46% a taxane; 39 of 41 EGFR-mutant patients had received targeted therapy.¹

The phase 3 AndroMETa Lung-167 trial (NCT07821684) is now comparing Temab-A with standard of care in pretreated EGFR wild-type nonsquamous NSCLC.^1,3

References

1. Sommerhalder D, Cho BC, Raimbourg J, et al. Overall survival analysis of telisotuzumab adizutecan (Temab-A) in patients with non-squamous non-small cell lung cancer: phase 1 first-in-human study. Presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract 2658RO.

2. A study to assess adverse events and pharmacokinetics of ABBV-400 in adult participants with advanced solid tumors. ClinicalTrials.gov identifier: NCT05029882. Updated 2026. Accessed October 30, 2026. https://clinicaltrials.gov/study/NCT05029882

3. A study to assess intravenous (IV) telisotuzumab adizutecan compared to standard of care in adult participants previously treated, EGFR wildtype, locally advanced/metastatic non-squamous non-small cell lung cancer. ClinicalTrials.gov identifier: NCT07821684. Updated 2026. Accessed October 30, 2026. https://clinicaltrials.gov/study/NCT07821684