ZYNLONTA in combination with glofitamab demonstrated clinically meaningful benefit with 94% best ORR and 72% CR rate
Safety data show no dose-limiting toxicities (DLTs), no high-grade cytokine release syndrome (CRS) or high-grade immune effector cell-associated neurotoxicity syndrome (ICANS) across all patients
Company to host conference call today at 8:30 a.m. EST
LAUSANNE, Switzerland I December 11, 2024 I ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), today announced positive initial data from the LOTIS-7 Phase 1b open-label clinical trial evaluating the safety and efficacy of ZYNLONTA® in combination with the bispecific antibody glofitamab (COLUMVI™) in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL).
“We are excited by the strong initial results observed with ZYNLONTA plus glofitamab in second line plus patients with relapsed or refractory DLBCL,” said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. “We believe these data support our hypothesis that combining these two potent, approved, single-agent-drugs with complementary mechanisms of action will yield additive or synergistic efficacy, and a manageable safety profile given no overlapping non-hematologic toxicities, enabling administration across care settings. We are encouraged by the initial promising safety and efficacy data at both doses tested in the expansion arm.”
Initial Clinical Data from Phase 1b LOTIS-7 Trial
LOTIS-7 is an ongoing Phase 1b global multicenter, multi-arm study in patients with relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) including Part 1 (dose escalation) and Part 2 (dose expansion). As of the November 20, 2024 cutoff date, a total of 29 B-NHL patients from Part 1 and Part 2 across all dose levels were treated and evaluated for safety.
An initial efficacy analysis was conducted on all 18 evaluable 2L+ DLBCL patients who received dose levels of 120 µg/kg (n=9) or 150 µg/kg (n=9) of ZYNLONTA plus the bispecific antibody glofitamab:
- Best overall response rate (ORR) was 94% (17/18) as assessed by Lugano criteria
- Complete response (CR) was achieved in 72% (13/18) and partial response (PR) was achieved in 22% (4/18) of patients. Of those achieving CR, 12 out of 13 remain in CR as of the cutoff date.
- Among patients treated with ZYNLONTA at the 150µg/kg dose (the initial dose approved for ZYNLONTA as a monotherapy in 3L+ DLBCL patients), best ORR was 100% (9/9) and CR was achieved in 78% (7/9) of patients
Encouraging efficacy data was observed across patients with different numbers of lines and types of prior treatments and across different histologies.
Initial safety data on all 29 patients suggest that ZYNLONTA plus glofitamab is generally well tolerated with no DLTs across all dose levels:
- Treatment emergent adverse events (TEAEs) of Grade 3 or higher occurring in ≥ 5% of patients included neutropenia (24%), lymphopenia (7%) and hypokalemia (7%)
- Cytokine Release Syndrome (CRS) of Grade 1 or 2 according to ASTCT grading was observed in 34.5% of patients and resolved with standard treatment. Low-grade Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) (Grade 2 according to ASTCT grading) was observed in two patients and both had complete resolution of symptoms. No Grade 3 or higher CRS or ICANS were observed.
- There were no Grade 5 TEAEs observed
“These compelling initial results support the potential of ZYNLONTA plus the bispecific glofitamab to be a best-in-class combination in a highly competitive market,” said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. “We look forward to completing enrollment of dose expansion in the first half of 2025 and plan to engage with regulatory authorities on the path forward as data including additional patients with longer follow-up become available.”
Conference Call Information
To access the conference call, please register here. The participant toll-free dial-in number is 1-800-836-8184 for North America and Canada. It is recommended that you join 10 minutes before the event, though you may pre-register at any time. A live webcast of the call will be available under “Events and Presentations” in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.
About LOTIS-7
LOTIS-7 is a Phase 1b global multicenter, multi-arm study in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) including Part 1 (dose escalation) and Part 2 (dose expansion). The three dosing arms include ZYNLONTA plus polatuzumab vedotin, ZYNLONTA plus glofitamab, and ZYNLONTA plus mosunetuzumab T-cell-engaging bispecific monoclonal antibodies (BsAbs). Enrollment in LOTIS-7 includes Part 1 of the study with a 3+3 dose escalation in 3L/3L+ heavily pre-treated patients with ZYNLONTA doses starting at 90 µg/kg and then proceeding to 120 µg/kg and 150 µg/kg. Part 2 includes dose expansion in 2L/2L+ large B-cell lymphoma in the ZYNLONTA plus glofitamab arm at dose levels determined from Part 1 (120 µg/kg and 150 µg/kg of ZYNLONTA plus the approved dosing of glofitamab). Primary endpoints of the study include safety and tolerability. Secondary efficacy endpoints include ORR, DOR, CRR, PFS, RFS, and OS as well as pharmacokinetics and immunogenicity.
For more information about the LOTIS-7 trial, visit clinicaltrials.gov (NCT04970901).
About ADC Therapeutics
ADC Therapeutics (NYSE: ADCT) is a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs). The Company is advancing its proprietary ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors.
ADC Therapeutics’ CD19-directed ADC ZYNLONTA (loncastuximab tesirine-lpyl) received accelerated approval by the FDA and conditional approval from the European Commission for the treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in development in combination with other agents and in earlier lines of therapy. In addition to ZYNLONTA, ADC Therapeutics has multiple ADCs in ongoing clinical and preclinical development.
ADC Therapeutics is based in Lausanne (Biopôle), Switzerland, and has operations in London and New Jersey. For more information, please visit https://adctherapeutics.com/ and follow the Company on LinkedIn.
ZYNLONTA® is a registered trademark of ADC Therapeutics SA.
SOURCE: ADC Therapeutics
Post Views: 66
ZYNLONTA in combination with glofitamab demonstrated clinically meaningful benefit with 94% best ORR and 72% CR rate
Safety data show no dose-limiting toxicities (DLTs), no high-grade cytokine release syndrome (CRS) or high-grade immune effector cell-associated neurotoxicity syndrome (ICANS) across all patients
Company to host conference call today at 8:30 a.m. EST
LAUSANNE, Switzerland I December 11, 2024 I ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), today announced positive initial data from the LOTIS-7 Phase 1b open-label clinical trial evaluating the safety and efficacy of ZYNLONTA® in combination with the bispecific antibody glofitamab (COLUMVI™) in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL).
“We are excited by the strong initial results observed with ZYNLONTA plus glofitamab in second line plus patients with relapsed or refractory DLBCL,” said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. “We believe these data support our hypothesis that combining these two potent, approved, single-agent-drugs with complementary mechanisms of action will yield additive or synergistic efficacy, and a manageable safety profile given no overlapping non-hematologic toxicities, enabling administration across care settings. We are encouraged by the initial promising safety and efficacy data at both doses tested in the expansion arm.”
Initial Clinical Data from Phase 1b LOTIS-7 Trial
LOTIS-7 is an ongoing Phase 1b global multicenter, multi-arm study in patients with relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) including Part 1 (dose escalation) and Part 2 (dose expansion). As of the November 20, 2024 cutoff date, a total of 29 B-NHL patients from Part 1 and Part 2 across all dose levels were treated and evaluated for safety.
An initial efficacy analysis was conducted on all 18 evaluable 2L+ DLBCL patients who received dose levels of 120 µg/kg (n=9) or 150 µg/kg (n=9) of ZYNLONTA plus the bispecific antibody glofitamab:
- Best overall response rate (ORR) was 94% (17/18) as assessed by Lugano criteria
- Complete response (CR) was achieved in 72% (13/18) and partial response (PR) was achieved in 22% (4/18) of patients. Of those achieving CR, 12 out of 13 remain in CR as of the cutoff date.
- Among patients treated with ZYNLONTA at the 150µg/kg dose (the initial dose approved for ZYNLONTA as a monotherapy in 3L+ DLBCL patients), best ORR was 100% (9/9) and CR was achieved in 78% (7/9) of patients
Encouraging efficacy data was observed across patients with different numbers of lines and types of prior treatments and across different histologies.
Initial safety data on all 29 patients suggest that ZYNLONTA plus glofitamab is generally well tolerated with no DLTs across all dose levels:
- Treatment emergent adverse events (TEAEs) of Grade 3 or higher occurring in ≥ 5% of patients included neutropenia (24%), lymphopenia (7%) and hypokalemia (7%)
- Cytokine Release Syndrome (CRS) of Grade 1 or 2 according to ASTCT grading was observed in 34.5% of patients and resolved with standard treatment. Low-grade Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) (Grade 2 according to ASTCT grading) was observed in two patients and both had complete resolution of symptoms. No Grade 3 or higher CRS or ICANS were observed.
- There were no Grade 5 TEAEs observed
“These compelling initial results support the potential of ZYNLONTA plus the bispecific glofitamab to be a best-in-class combination in a highly competitive market,” said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. “We look forward to completing enrollment of dose expansion in the first half of 2025 and plan to engage with regulatory authorities on the path forward as data including additional patients with longer follow-up become available.”
Conference Call Information
To access the conference call, please register here. The participant toll-free dial-in number is 1-800-836-8184 for North America and Canada. It is recommended that you join 10 minutes before the event, though you may pre-register at any time. A live webcast of the call will be available under “Events and Presentations” in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.
About LOTIS-7
LOTIS-7 is a Phase 1b global multicenter, multi-arm study in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) including Part 1 (dose escalation) and Part 2 (dose expansion). The three dosing arms include ZYNLONTA plus polatuzumab vedotin, ZYNLONTA plus glofitamab, and ZYNLONTA plus mosunetuzumab T-cell-engaging bispecific monoclonal antibodies (BsAbs). Enrollment in LOTIS-7 includes Part 1 of the study with a 3+3 dose escalation in 3L/3L+ heavily pre-treated patients with ZYNLONTA doses starting at 90 µg/kg and then proceeding to 120 µg/kg and 150 µg/kg. Part 2 includes dose expansion in 2L/2L+ large B-cell lymphoma in the ZYNLONTA plus glofitamab arm at dose levels determined from Part 1 (120 µg/kg and 150 µg/kg of ZYNLONTA plus the approved dosing of glofitamab). Primary endpoints of the study include safety and tolerability. Secondary efficacy endpoints include ORR, DOR, CRR, PFS, RFS, and OS as well as pharmacokinetics and immunogenicity.
For more information about the LOTIS-7 trial, visit clinicaltrials.gov (NCT04970901).
About ADC Therapeutics
ADC Therapeutics (NYSE: ADCT) is a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs). The Company is advancing its proprietary ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors.
ADC Therapeutics’ CD19-directed ADC ZYNLONTA (loncastuximab tesirine-lpyl) received accelerated approval by the FDA and conditional approval from the European Commission for the treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in development in combination with other agents and in earlier lines of therapy. In addition to ZYNLONTA, ADC Therapeutics has multiple ADCs in ongoing clinical and preclinical development.
ADC Therapeutics is based in Lausanne (Biopôle), Switzerland, and has operations in London and New Jersey. For more information, please visit https://adctherapeutics.com/ and follow the Company on LinkedIn.
ZYNLONTA® is a registered trademark of ADC Therapeutics SA.
SOURCE: ADC Therapeutics
Post Views: 66
