Temab-A Displays Early Efficacy in Locally Advanced/Metastatic PDAC

Treatment with telisotuzumab adizutecan (ABBV-400; Temab-A), a c-Met protein-targeting antibody drug conjugate (ADC), exhibited promising antitumor activity and a manageable safety profile among patients with previously treated, locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), according to findings from a phase 1 basket study (NCT06084481) presented at the European Society for Medical Oncology (ESMO) Congress 2025.

Specifically, among 42 patients with this disease treated with Temab-A in the second-line setting, a confirmed objective response rate (cORR) of 23.8% was observed. Furthermore, the agent conferred a confirmed clinical benefit rate (cCBR) of 81.0% and the median duration of response (DOR) was 6.9 months. The median progression-free survival (PFS) was 5.4 months, with 73.8% of patients experiencing progression during the study period, and the median overall survival (OS) was 7.9 months, with 54.8% having died as of data cutoff.

Among patients who received prior leucovorin (folinic acid), 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) in the first-line setting (n = 26), the cORR was 15.4% and the cCBR was 80.8%. The median PFS and OS were 5.0 months and 7.1 months, with 73.1% having progressed and 57.7% having died as of data cutoff.

For those previously treated with gemcitabine and nab-paclitaxel in the first-line setting, the cORR and cCBR were 40.0% and 80.0%, respectively. Additionally, the median PFS and OS were 6.3 months and 11.6 months, respectively, with 80.0% of patients having progressed and 53.3% of patients having died as of data cutoff.

“PDAC tumors are characterized by c-Met expression. Temab-A [showed] anti-tumor activity in this population, which requires further evaluation in larger prospective studies. The safety profile is consistent with that of prior phase 1 studies,” presenting investigator James J Harding, MD, an associate attending physician, gastrointestinal medical oncologist, and early drug specialist at Memorial Sloan Kettering Cancer Center, said in the presentation of the data.

The phase 1 basket study enrolled patients 18 years and older with numerous advanced solid tumor types and assigned them to 9 cohorts based on tumor type. The main inclusion criteria for the PDAC cohort—the one assessed in the presentation—included being biomarker unselected and having histologically or cytologically confirmed disease. Patients must have experienced progression during or after first-line treatment, and had an ECOG performance status of 0 or 1. Neoadjuvant or adjuvant chemotherapy was permitted if recurrence occurred within 6 months of treatment.

Those treated for PDAC received 2.4 or 3.0 mg/kg of Temab-A on a triweekly dosing schedule. Following a safety monitoring committee decision, the dose of Temab-A was reduced from 3.0 mg/kg to 2.4 mg/kg, with 13 and 29 patients receiving each dose, respectively, at the start of treatment.

Among patients enrolled on trial, the median age was 69 years (range, 45-86), and most patients were male (57%) and White (86%). Patients mostly had an ECOG performance status of 1 (57%), metastasis at baseline (88%), and received FOLFIRINOX as first-line therapy in the locally advanced setting (62%). The median number of years from initial diagnosis was 1.2 (range, 0.3-6.3), patients received a median of 1 (range, 1-3) prior line of systemic therapy, and 29% of patients had received prior radiotherapy in addition to chemotherapy.

The primary end point of the study was investigator-assessed cORR per RECIST v1.1 criteria. Secondary end points included DOR, CBR, PFS, OS, and safety.

A median treatment duration of 4.3 months (range, 0.7-14.3) was observed with Temab-A; the median relative dose intensity was 90% (range, 64%-100%). Treatment-emergent adverse effects (TEAEs) of any grade, of grade 3 or higher, or deemed serious occurred in 100%, 81%, and 52% of patients. Treatment-related AEs (TRAEs) of any grade occurred in 93% of patients, TRAEs of grade 3 or higher occurred in 57% of patients, and TRAEs that were deemed serious occurred in 19% of patients.

The most common hematologic AEs of any grade and grade 3 or higher in severity included anemia (50% and 38%), neutropenia (43% and 24%), leukopenia (19% and 7%), lymphopenia (12% and 7%), and thrombocytopenia (12% and 5%). The most common non-hematologic AEs included nausea (55% and 0%), decreased appetite (48% and 2%), fatigue (41% and 2%), vomiting (36% and 0%), and peripheral edema (26% and 2%).

TRAEs leading to dose reduction, dose interruption, or treatment discontinuation occurred in 48%, 38%, and 14% of patients, respectively. Additionally, the adjudicated interstitial lung disease/pneumonitis rate was 4.8%, with single instances of grade 2 or grade 3 events reported.

Furthermore, an immunohistochemical analysis found that all tumor tissues analyzed had c-Met protein staining with 2+ and/or 3+ intensity. Investigators noted that c-Met expression prevalence was consistent between diagnostic and recently obtained samples, and that the relationship between c-Met expression and response to treatment warranted further evaluation.

Reference

Harding JJ, Strickler J, Henry J, et al. Phase 1 basket study of telisotuzumab adizutecan (ABBV-400; Temab-A), a c-Met protein–targeting antibody-drug conjugate: results from patients with pancreatic ductal adenocarcinoma. Presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 2214MO.