EQS Group-News: ADC Therapeutics SA / Key word(s): Conference
ADC Therapeutics Presents Updated Data from Clinical Trials of Novel Antibody Drug Conjugates
ADCT-402 (loncastuximab tesirine) continues to demonstrate acceptable safety profile and anti-tumor activity in patients with relapsed or refractory diffuse large B-cell lymphoma; data from 183-patient study supports continued evaluation in ongoing pivotal Phase II trial
ADCT-301 (camidanlumab tesirine) achieves 86.5 percent overall response rate in heavily pretreated patients with Hodgkin lymphoma; data from 113-patient study supports further investigation in pivotal Phase II trial
Data presented at 60th American Society of Hematology (ASH) Annual Meeting
"We are encouraged by the safety profiles and strong single-agent anti-tumor activity we continue to observe in the 183-patient first-in-human clinical trial of ADCT-402 and the 113-patient trial of ADCT-301," said Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics. "The updated ADCT-402 data presented at ASH support its continued evaluation in our ongoing pivotal clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma. For ADCT-301, we now have the dosing data to support further investigation in a planned pivotal Phase II trial in patients with relapsed or refractory Hodgkin lymphoma, which we look forward to initiating in 2019."
- ADCT-402 has demonstrated manageable toxicity in patients with R/R DLBCL
- At doses >120 µg/kg, the overall response rate (ORR) was 43.3% (55/127 patients with DLBCL), comprising 23.6% complete responses and 19.7% partial responses
- At doses >120 µg/kg, after a median follow up of 5.5 months, median duration of response (DoR) was not reached in patients achieving a complete response
A pivotal Phase II study is currently enrolling patients with R/R DLBCL to evaluate the efficacy and safety of ADCT-402 at dose 150 µg/kg every three weeks for two cycles followed by dose 75 µg/kg every three weeks (NCT03589469).
- ADCT-402 has demonstrated manageable toxicity in patients with R/R FL and R/R MCL
- In patients with FL, ORR was 78.6% (11/14) and median DoR was not reached after a median follow-up time of 11.6 months
- In patients with MCL, ORR was 46.7% (7/15) and median DoR was not reached after a median follow-up time of 8.7 months
Key findings from the oral presentation include:
- ADCT-301 has demonstrated manageable toxicity in patients with R/R HL
- The most common Grade 3 or 4 treatment-emergent adverse events occurring in at least 5 percent of patients, regardless of attribution, at the 45 µg/kg dose in 37 patients were: maculopapular rash (18.9 percent),elevated gamma-glutamyltransferase (8.1 percent), elevated alanine aminotransferase (8.1 percent), elevated aspartate aminotransferase (2.7 percent), anemia (8.1 percent), Guillain-Barré syndrome / radiculopathy (8.1 percent) and increased lipase (8.1 percent)
- In patients with R/R HL, therapy with ADCT-301 achieved an overall response rate (ORR) of 86.5% in the 37 patients in the 45 µg/kg dose group who had received and failed prior brentuximab vedotin and most of whom had failed prior checkpoint inhibitor treatment
- These data support further investigation of the 45 µg/kg dose of ADCT-301 in a planned pivotal Phase II study anticipated to commence in 2019
- ADCT-301 demonstrated an acceptable safety profile during dose-escalation
- Overall, in patients with R/R NHL, therapy with ADCT-301 achieved an ORR of 31.7% (13/41) at doses >60 µg/kg
- In the R/R T-cell lymphoma subgroup, therapy with ADCT-301 achieved an ORR of 53.8% (7/13) in the 60 and 80 µg/kg dose groups
- These data support further investigation of ADCT-301 in T-cell lymphoma
ADCT-402 (loncastuximab tesirine) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death. ADCT-402 is being evaluated in a pivotal Phase II clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (NCT03589469). The U.S. Food and Drug Administration granted orphan drug designation to ADCT-402 for the treatment of DLBCL and mantle cell lymphoma.
ADCT-301 (camidanlumab tesirine) is an antibody drug conjugate (ADC) composed of a monoclonal antibody that binds to CD25 (HuMax(R)-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload tesirine. Once bound to a CD25-expressing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead. The intra-tumor release of its PBD warhead may cause bystander killing of neighboring tumor cells. In addition, the PBD warhead will trigger immunogenic cell death, which in turn will strengthen the immune response against tumor cells. ADCT-301 is being evaluated in ongoing Phase Ia/Ib clinical trials in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma (NCT02432235), as well as a Phase Ib clinical trial in solid tumors (NCT03621982).
Document title: ADCT_ASH 2018 Data_5.12.2018
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