Preliminary results of an ongoing dose-escalation and expansion phase 1 (Duet 1; NCT03411915) trial indicate that the anti–somatostatin receptor type 2 (SSTR2) × anti-CD3 bispecific antibody XmAb18087 was well-tolerated and accompanied by sustained T-cell activation in patients with advanced neuroendocrine tumors (NETs).
Given that SSTR2 is highly overexpressed in NETs, the anti-SSTR2 × anti-CD3 bispecific antibody XmAb18087 (tidutamab) has been developed to trigger T-cell–mediated cytotoxicity specifically in SSTR2+ NET cells. The ongoing dose-escalation and expansion phase 1 Duet-1 study (NCT03411915) is investigating the safety, pharmacokinetic/pharmacodynamic, and antitumor activity of XmAb18087 in patients with advanced NETs and gastrointestinal stromal tumors. Preliminary results of the Duet-1 trial for the NET cohorts were reported at the 2020 North American Neuroendocrine Tumor Society Annual Symposium.
Eligibility criteria included patients with histologically or cytologically confirmed grade 1 or 2 NET of pancreatic, gastrointestinal, lung, or undetermined origin, that was unresectable, locally advanced, or metastatic; had progressed on or was ineligible for somatostatin analogs (SSAs) and ≥1 other targeted therapies; and had disease progression within the past 12 months. XmAb18087 was administered as weekly infusions on days 1, 8, 15, and 22 in 28-day cycles, in parallel cohorts of patients (first dose, 0.1-1.0 µg/kg; thereafter, 0.1-2.0 µg/kg). Patients received prophylaxis for cytokine release syndrome (CRS), as well as nausea and vomiting at least through cycle 1.
At data cutoff (August 26, 2020), 27 patients had received ≥1 doses of XmAb18087 and were included in the analysis; of these, 21 were in the dose-escalation phase and 6 were in the expansion phase at the maximum tolerated dose, which was established as 0.3 µg/kg priming dose and 1.0 µg/kg repeating dose. A total of 24 patients discontinued treatment, 12 because of disease progression and 4 because of adverse events (AEs).
The median patient age was 61 years; 56% were male. Primary tumors were located in the pancreas (56%), lung (15%), and intestine (15%), and were grade 2 in the majority of patients (58%). Patients had received a median of 4 prior disease-specific systemic therapies; 56% of patients had received peptide receptor radionuclide therapy and 41% continued receiving an SSA while participating in the study.
Dose-limiting toxicities were nausea and vomiting that occurred at 1.0→2.0 µg/kg. Grade 3/4 treatment-related AEs occurred in 63% of patients, and no deaths were reported. CRS occurred in 11 patients, and was mostly grade 1/2 and decreased after the first 2 doses. Grade 3/4 lymphopenia occurred in 41% of patients; however, it had no apparent deleterious clinical effects. Of the 14 patients evaluable for response, the best response was stable disease in 6 (43%) patients, with a median treatment duration of 7 months. Pharmacokinetic analysis of XmAb18087 demonstrated dose-proportional pharmacokinetic at priming and repeating doses, with a median half-life of 94 hours, which supports weekly dosing. XmAb18087 treatment induced acute and sustained T-cell activation in peripheral blood.
The preliminary results of the Duet-1 trial indicate that XmAb18087 was well-tolerated and accompanied by sustained T-cell activation in patients with NETs; further studies and longer follow-up are warranted to further define the therapeutic role of XmAb18087 in this patient population.
Source: El-Rayes B, et al. North American Neuroendocrine Tumor Society 2020 Annual Symposium; October 1-3, 2020. Abstract C1.
To sign up for our newsletter or print publications, please enter your contact information below.
