Benzinga | Dec 7, 2020 07:08AM EST

ADC Therapeutics Announces Updated Clinical Data on Lead Antibody Drug Conjugate Programs Loncastuximab Tesirine (Lonca) and Camidanlumab Tesirine (Cami) Presented at 62nd American Society of Hematology Annual Meeting

Lonca LOTIS 2 subgroup data include updated median duration of response of 12.58 months

LOTIS 3 interim results highlight potential of Lonca in combination with ibrutinib in relapsed or refractory diffuse large B-cell lymphoma and mantle cell lymphoma patients

Preliminary pivotal Cami data demonstrate 83% overall response rate and no new safety signals in patients with relapsed or refractory Hodgkin lymphoma

Company to host conference call and webcast today at 8 a.m. ET

LAUSANNE, Switzerland--(BUSINESS WIRE)-- ADC Therapeutics SA (NYSE:ADCT), a late clinical-stage oncology-focused biotechnology company pioneering the development and commercialization of highly potent and targeted antibody drug conjugates (ADCs) for patients with hematological malignancies and solid tumors, today announced updated clinical data from its two lead programs, loncastuximab tesirine (Lonca) and camidanlumab tesirine (Cami), which were presented at the 62nd American Society of Hematology (ASH) Annual Meeting.

"The encouraging data presented at the 2020 ASH Annual Meeting reinforce the significant progress we have made with our PBD-based ADCs for patients with hematological malignancies," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "The U.S. Food and Drug Administration recently accepted our Biologics License Application for Lonca for the treatment of relapsed or refractory diffuse large B-cell lymphoma and granted priority review status with a Prescription Drug User Fee Act (PDUFA) target date of May 21, 2021, based on the data from our pivotal LOTIS 2 clinical trial. As we rigorously prepare for potential approval and launch in 2021, we look forward to continuing to evaluate the potential of Lonca, as a single agent and in combination, in heavily pretreated patients, in earlier lines of therapy and in additional indications such as follicular lymphoma. As for Cami, our pivotal Phase 2 trial in Hodgkin lymphoma is now more than 50 percent enrolled, and the preliminary data presented at ASH highlight its potential to address an unmet need in heavily pretreated Hodgkin lymphoma patients."

Lonca LOTIS 2 Subgroup Analysis (Abstract 1183)

In LOTIS 2, a single-arm, open-label, 145-patient Phase 2 clinical trial in patients with relapsed or refractory DLBCL who had failed ?2 established therapies, Lonca demonstrated substantial antitumor activity and an acceptable safety profile. Updated results, including analysis of response in subgroups with high risk of poor prognosis, were presented in a poster at ASH 2020 by Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University.

Key data at the August 6, 2020, data cut include:

* Overall response rate (ORR) was 48.3% and complete response rate (CRR) was 24.8%

* Median duration of response (mDoR) of 12.58 months for the 70 responders, and mDoR of 13.37 months for patients achieving a complete response

* Durable responses in high-risk patient groups, including: Those who had progression after prior CAR-T therapy: ORR was 46.2% (6/13 patients) Double or triple hit: ORR was 33.3% (5/15 patients) Transformed DLBCL: ORR was 44.8% (13/29 patients)

* No new safety concerns were identified during the study and no increase in toxicity was observed in patients aged ?65 years compared with younger patients

Lonca LOTIS 3 Interim Results (Abstract 2099)

LOTIS 3, a Phase 1/2, two-part, open-label, single-arm clinical trial that is intended to support the submission of a Biologics License Application, is evaluating Lonca in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma (MCL). Updated interim data for patients receiving the 60 ?g/kg Phase 2 dose of Lonca every three weeks and ibrutinib 560 mg/day were presented in a poster at ASH 2020. As of the data cut-off date of August 20, 2020, 37 patients had received the Phase 2 dose and 35 were evaluable for efficacy.

Key data include:

* ORR in all patients was 62.9% In non-germinal center B-cell DLBCL patients, ORR was 66.7% (16/24 patients) and CRR was 37.5% (9/24 patients) In germinal center B-cell DLBCL patients, ORR was 20% (1/5 patients) In all DLBCL patients, ORR was 58.6% (17/29 patients) In all MCL patients, ORR was 83.3% (5/6 patients)

* Lonca in combination with ibrutinib had manageable toxicity, with the most common grade ?3 treatment-emergent adverse events (TEAEs) in ?5% of patients being anemia (10.8%), neutropenia (10.8%), thrombocytopenia (5.4%), and fatigue (5.4%)

* Pharmacokinetic profiles demonstrated good Lonca exposure coverage throughout the dosing interval

"The need for a later line of therapy that is both effective and tolerable is underscored by the significant number of patients with DLBCL or MCL who relapse after treatment and have a poor prognosis," said Julien Depaus, MD, Department of Hematology, CHU UCL Namur. "It is very encouraging to see that Lonca in combination with ibrutinib, at the Phase 2 dose identified as the maximum tolerated dose in the initial Phase 1 portion of the clinical trial, continues to demonstrate antitumor activity and manageable toxicity in patients with relapsed or refractory DLBCL and MCL."

Cami Pivotal Phase 2 Preliminary Results (Abstract 474)

Cami is being evaluated in a multicenter, open-label, single-arm, 100-patient Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma (HL) who have received ?3 prior lines of treatment (?2 lines if ineligible for hematopoietic stem cell transplantation, HSCT) including prior treatment with brentuximab vedotin and a checkpoint inhibitor. Preliminary efficacy and safety data were reported in an oral presentation at ASH 2020. As of the data cut-off date of August 24, 2020, 51 patients had been treated with Cami and the median number of Cami cycles was five.

Key data include:

* ORR was 83% (39/47 patients) and CRR was 38.3% (18/47 patients)

* Five patients (10.6%) went on to consolidation with HSCT

* No new safety signals have been identified and the most common grade ?3 TEAEs in ?5% of patients were hypophosphatemia (11.8%), gamma-glutamyltransferase increased (9.8%), alanine aminotransferase increased (5.9%), and maculopapular rash (5.9%)

* Three cases of Guillain-Barr? syndrome have been reported

"Patients with relapsed or refractory HL who do not respond, or experience disease progression after initial response, to treatments such as brentuximab vedotin and PD-1 blockade have limited therapeutic options," said Alex Herrera, MD, Assistant Professor, Department of Hematology and Hematopoietic Cell Transplantation at City of Hope Medical Center. "The encouraging antitumor activity Cami has demonstrated as a single agent and its safety profile, which has been consistent with the Phase 1 trial, warrant the continued evaluation of this CD25-targeted ADC in relapsed or refractory HL patients."

ADC Therapeutics anticipates reporting interim results from the pivotal Phase 2 trial of Cami in HL in the first half of 2021. A Phase 1b clinical trial of Cami as monotherapy or in combination with pembrolizumab is currently enrolling patients with selected advanced solid tumors.