2016 AACR Annual Meeting
© AACR/Todd Buchanan
NEW ORLEANS—Administering an antibody-radionuclide conjugate after B-cell depletion with rituximab can produce lasting responses in patients with relapsed non-Hodgkin lymphoma (NHL), according to a phase 1/2 study.
The conjugate, 177Lu-DOTA-HH1 (Betalutin), consists of the tumor-specific antibody HH1, which targets the CD37 antigen on the surface of NHL cells, conjugated to the β-emitting isotope lutetium-177 (Lu-177) via the chemical linker DOTA.
In an ongoing phase 1/2 study, Betalutin given after rituximab produced an overall response rate of 63.2%.
The median duration of response has not yet been reached, and 1 patient has maintained a response for more than 36 months.
In addition, the researchers said Betalutin was well tolerated, with a predictable and manageable safety profile. Most adverse events were hematologic, and all have been transient and reversible.
These results were presented at the 2016 AACR Annual Meeting (abstract LB-252*). The study is sponsored by Nordic Nanovector ASA.
Patients and study design
The researchers presented data on 21 patients—19 with follicular lymphoma and 2 with mantle cell lymphoma. All tumors were positive for CD37.
The patients’ median age was 68 (range, 41-78). Sixty-seven percent were male, and they had received 1 to 8 prior treatment regimens.
In this dose-escalation study, patients received Betalutin at 3 different doses, but they were also divided into 2 arms according to predosing with cold HH1 antibody.
In Arm 1 (n=12), patients received rituximab (at 375 mg/m2) on day -28 and -21 to deplete circulating B cells. On day 0, predosing with 50 mg HH1 was given before Betalutin injection. Then, patients received Betalutin at 10 MBq/kg (n=3), 15 MBq/kg (n=6), or 20 MBq/kg (n=3).
In Arm 2 (n=4), patients received rituximab at the same dose and schedule as Arm 1, but Betalutin was administered without HH1 predosing on day 0 at either 10 MBq/kg (n=2) or 15 MBq/kg (n=2).
The first patient treated on this trial received 250 mg/m2 of rituximab on day -7 and day 0 prior to Betalutin administration and was included in the 10 MBq/kg group in Arm 2.
The 15 MBq/kg dose level of Arm 1 has been expanded into the phase 2 portion of the study, as dose-limiting toxicities occurred at the 20 MBq/kg dose. Five patients have been treated in the phase 2 portion.
Safety
Adverse events (AEs) from the phase 2 portion of the study were not reported, as the data are still being collected.
In the phase 1 portion, grade 3/4 AEs were hematologic in nature and included decreases in platelet counts (3 grade 3 and 6 grade 4) and neutrophil counts (5 grade 3 and 4 grade 4).
Serious AEs included decreases in platelet counts (n=2), atrial fibrillation (n=2), epistaxis (n=1), fractured sternum (n=1), decreased neutrophil count (n=1), pharyngitis (n=1), pneumonia (n=1), pulmonary embolism (n=1), and sepsis (n=1).
The pulmonary embolism was deemed unrelated to treatment, but the remaining events were considered possibly or probably related to Betalutin.
The researchers noted that 1 patient experienced pharyngitis, pneumonia, pulmonary embolism, epistaxis, sepsis, and a decrease in lymphocyte count.
All patients’ platelets and neutrophils recovered. Two patients required platelet transfusions—one patient in the 20 MBq/kg cohort of Arm 1 and one patient in the 15 MBq/kg cohort of Arm 2.
Efficacy
Nineteen patients were evaluable for response. The overall response rate was 63.2% (n=12) and included both complete (31.6%, n=6) and partial responses (31.6%, n=6). Progression occurred in 21.1% of patients (n=4), and 15.8% (n=3) had stable disease.
The researchers presented data on 9 patients treated at the recommended 15 MBq/kg dose level with 50 mg HH1 predosing. Five patients were treated in phase 1 and 4 in phase 2. One of these patients was excluded from the analysis due to transformed lymphoma.
Two patients in phase 1 responded—both complete responses—and 3 patients in phase 2 responded—2 complete and 1 partial response.
For the entire study cohort, the median duration of response has not yet been reached. Six responses are ongoing—2 for 3+ months, 1 for 6+ months, 1 for 18+ months, 1 for 24+ months, and 1 for 36+ months.
*Information in the abstract differs from that presented at the meeting.