ADC Therapeutics Presents Updated ZYNLONTA™ (loncastuximab tesirine-lpyl) Clinical Data at 16th Annual International Conference on Malignant Lymphoma

Rhea-AI Summary

ADC Therapeutics (NYSE:ADCT) announced the presentation of updated results from four clinical trials of ZYNLONTA™ (loncastuximab tesirine-lpyl) at the 16th Annual International Conference on Malignant Lymphoma (ICML). Key findings from the LOTIS-2 trial showed an overall response rate (ORR) of 48.3% and a median duration of response (mDoR) of 13.4 months in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The LOTIS-3 trial results reflected a 62.2% ORR when ZYNLONTA was combined with ibrutinib, with manageable toxicity. The company anticipates continued progress in ongoing clinical trials.

Positive

• LOTIS-2 trial reported an overall response rate (ORR) of 48.3% for ZYNLONTA in relapsed/refractory DLBCL.
• LOTIS-2 median duration of response (mDoR) was 13.4 months.
• LOTIS-3 trial showed an ORR of 62.2% for ZYNLONTA in combination with ibrutinib.

Negative

• No significant negative business aspects identified.

ADC Therapeutics SA (NYSE:ADCT), a commercial-stage biotechnology company leading the development of novel antibody drug conjugates (ADCs) to treat hematological malignancies and solid tumors, announced today that posters on four ZYNLONTA™ (loncastuximab tesirine-lpyl) clinical trials were presented at the 16^th Annual International Conference on Malignant Lymphoma (ICML).

“The updated results from our pivotal LOTIS-2 clinical trial presented at ICML continue to reinforce the efficacy across difficult-to-treat subgroups and sustained duration of response of commercially-available ZYNLONTA as a single agent for patients with relapsed or refractory diffuse large B-cell lymphoma,” said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. “We’re also pleased that the updated data from the LOTIS-3 clinical trial demonstrate the encouraging antitumor activity and manageable toxicity profile of ZYNLONTA in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma. We look forward to continued progress in all of our LOTIS trials, including the ongoing LOTIS-5 trial of ZYNLONTA in combination with rituximab and LOTIS-6 trial in patients with relapsed or refractory follicular lymphoma.”

LOTIS-2 Follow-up Analysis (Poster 177)

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, ZYNLONTA demonstrated continued substantial antitumor activity and an acceptable safety profile. Updated results were presented in a poster by Pier Luigi Zinzani, MD, PhD, IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, Italy. As of the data cut-off date of March 1, 2021, all patients had completed treatment.

Key data include:

• Overall response rate (ORR) was 48.3% and complete response rate (CRR) was 24.8%
• Median duration of response (mDoR) of 13.4 months for the 70 responders
• Median duration of response not reached for patients with a complete response
• Median overall survival was 9.5 months
• No new safety concerns were identified during the study and no increase in toxicity was observed in patients aged ≥65 years compared with patients <65 years. The most common grade ≥3 treatment-emergent adverse events (TEAEs) were neutropenia (26.2%), thrombocytopenia (17.9%), increased gamma-glutamyltransferase (17.2%), and anemia (10.3%)

LOTIS-3 Updated Phase 1 Results (Poster 238)

LOTIS-3, a Phase 1/2, two-part, open-label, single-arm clinical trial, is evaluating ZYNLONTA in combination with ibrutinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL). Updated Phase 1 results were presented in a poster by Julien Depaus, MD, Department of Hematology, CHU UCL Namur site Godinne, Yvoir, Belgium. As of the data cut-off date of March 1, 2021, 30 patients with DLBCL (24 with non-germinal center B-cell (non-GCB) DLBCL and 6 with GCB DLBCL) and 7 patients with MCL were included in the study.

Key data include:

• ORR in all patients was 62.2% and CRR was 35.1%
  • In non-GCB DLBCL patients, ORR was 66.7%
  • In GCB DLBCL patients, ORR was 16.7%
  • In MCL patients, ORR was 85.7%
• ZYNLONTA in combination with ibrutinib had manageable toxicity, with the most common grade ≥3 TEAEs in ≥5% of patients being anemia (10.8%), neutropenia (10.8%), thrombocytopenia (5.4%), and fatigue (5.4%)
• Pharmacokinetic profiles demonstrated sustained exposure and modest accumulation by Cycle 2

Two additional posters presented at the 16^th Annual ICML

• Phase 3 Randomized Study of Loncastuximab Tesirine plus Rituximab versus Immunochemotherapy in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma - LOTIS-5 (Poster 251)
• A Phase 2 Randomized Study of Loncastuximab Tesirine (Lonca) Versus (Vs) Idelalisib in Patients (Pts) with Relapsed or Refractory (R/R) Follicular Lymphoma (FL) - LOTIS-6 (Poster 264)

About ZYNLONTA™ (loncastuximab tesirine-lpyl)

ZYNLONTA™ is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death. The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA approval was based on data from LOTIS-2, a large (n=145) Phase 2 multinational, single-arm clinical trial of ZYNLONTA for the treatment of adult patients with r/r DLBCL following two or more prior lines of systemic therapy. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with very difficult to treat disease, including patients with high-grade B-cell lymphoma. The trial also enrolled patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, and patients who had stem cell transplants and CAR-T therapy prior to their treatment with ZYNLONTA. Results from the trial demonstrated an overall response rate (ORR) of 48.3% (70/145 patients), which included a complete response (CR) rate of 24.1% (35/145 patients) and a partial response (PR) rate of 24.1% (35/145 patients). Patients had a median time to response of 1.3 months. At the most recent data cut-off for patients enrolled in the trial, the median duration of response (mDoR) was 13.4 months. In a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, gamma-glutamyltransferase increased, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea and musculoskeletal pain. In LOTIS-2, the most common (≥10%) grade ≥3 treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), gamma-glutamyltransferase increased (17.2%) and anemia (10.3%).

ZYNLONTA is being evaluated in combination for earlier lines of therapy and as a monotherapy in other B-cell malignancies.

About ADC Therapeutics

ADC Therapeutics (NYSE:ADCT) is a commercial-stage biotechnology company improving the lives of cancer patients with its next-generation, targeted antibody drug conjugates (ADCs). The Company is advancing its proprietary PBD-based ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors.

ADC Therapeutics’ CD19-directed ADC ZYNLONTA™ (loncastuximab tesirine-lpyl) is approved by the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in late-stage clinical trials in combination with other agents. Cami (camidanlumab tesirine) is being evaluated in a late-stage clinical trial for relapsed or refractory Hodgkin lymphoma and in a Phase 1b clinical trial for various advanced solid tumors. In addition to ZYNLONTA and Cami, the Company has multiple PBD-based ADCs in ongoing clinical and preclinical development.

ADC Therapeutics is based in Lausanne (Biopôle), Switzerland and has operations in London, the San Francisco Bay Area and New Jersey. For more information, please visit https://adctherapeutics.com/ and follow the Company on Twitter and LinkedIn.

ZYNLONTA™ is a trademark of ADC Therapeutics SA.

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FAQ

What were the results of the LOTIS-2 trial for ADCT's ZYNLONTA?

The LOTIS-2 trial showed an overall response rate of 48.3% and a median duration of response of 13.4 months in patients with relapsed/refractory diffuse large B-cell lymphoma.

How did ZYNLONTA perform in the LOTIS-3 trial?

In the LOTIS-3 trial, ZYNLONTA combined with ibrutinib demonstrated a 62.2% overall response rate.

What is the significance of the presentations at ICML for ADCT?

The presentations reinforce ZYNLONTA's efficacy and safety, supporting its ongoing clinical development in difficult-to-treat cancers.

What are the next steps for ADCT following the ICML presentation?

ADCT plans to progress with ongoing trials, including LOTIS-5 and LOTIS-6, evaluating ZYNLONTA in combination therapies.

What is ZYNLONTA used to treat?

ZYNLONTA is approved for treating adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy.