Managing Editor, OncLive®
Kristi Rosa joined MJH Life Sciences in 2016 and has since held several positions within the company. She helped launch the rapidly growing infectious disease news resource Contagion, strengthened the Rare Disease Report, of HCPLive, and now serves as the main digital news writer for OncLive. Prior to working at the company, she served as lead copywriter and marketing coordinator at The Strand Theater. Email: firstname.lastname@example.org
The FDA has lifted a partial clinical hold that was placed on the phase 2 clinical trial of camidanlumab tesirine in patients with relapsed/refractory Hodgkin lymphoma.
The FDA has lifted a partial clinical hold that was placed on the phase 2 clinical trial (NCT04052997) of camidanlumab tesirine (formerly known as ADCT-301) in patients with relapsed/refractory Hodgkin lymphoma, according to ADC Therapeutics, the drug developer.1
The trial is intended to support the biotechnology company’s submission of a biologics license application for the novel antibody-drug conjugate (ADC) to the FDA.
“The ADC Therapeutics team worked diligently to provide a thorough and prompt response to the FDA following its request for information about our pivotal phase 2 clinical trial of [camidanlumab tesirine],” stated Jay Feingold, MD, PhD, senior vice president and chief medical officer of ADC Therapeutics in a recent press release. “During the partial clinical hold, we continued to treat patients benefiting from [camidanlumab tesirine], and now look forward to resuming the enrollment of new patients in the trial as soon as possible.”
Camidanlumab tesirine is composed of a monoclonal antibody that binds to CD25, which is conjugated to the pyrrolobenzodiazepine (PBD) dimer payload, tesirine. Once it is bound to the CD25-expressing cell, the ADC is adopted into the cell; there, enzymes release PBD-based warhead, which results in immunogenic cell death. The intratumoral release of the PBD warhead is also thought to cause bystander killing of neighboring tumor cells.
The multicenter, open-label, single-arm phase 2 trial is examining the safety and the efficacy of the ADC in patients with relapsed/refractory Hodgkin lymphoma. To be eligible for enrollment, patients had to have pathologically confirmed relapsed/refractory disease and have failed 3 prior lines of treatment, including brentuximab vedotin (Adcetris) and a checkpoint inhibitor approved for Hodgkin lymphoma treatment, such as nivolumab (Opdivo) or pembrolizumab (Keytruda).
Each participant enrolled on the trial will undergo a screening period of up to 28 days, a treatment period in 3-week cycles, and a follow-up period consisting of approximately every-12-week visits for up to 3 years following treatment discontinuation.2
Patients can continue treatment until disease progression, unacceptable toxicity, other discontinuation criteria, or for up to 1 year, whichever occurs first. Moreover, patients who experience clinical benefit at 1 year have the opportunity to potentially continue treatment following a case by case review with the trial sponsor.
The primary end point of the trial is objective response rate, and secondary end points include duration of response, complete response, relapse-free survival, progression-free survival, and overall survival, among others.
Interim data from a first-in-human clinical trial (NCT02432235) of the ADC in a subgroup of patients with relapsed/refractory Non-Hodgkin lymphoma were previously reported at the 2018 ASH Annual Meeting and indicated an acceptable safety profile.3
At the time of the presentation, a total of 44 patients with Non-Hodgkin lymphoma had been enrolled on the trial. Participants were treated with the ADC at doses ranging from 3 µg/kg to 150 µg/mg. The median number of cycles was 2 and the median treatment duration was 22 days. Based on pharmacokinetic data collected from 34 patients, exposure was dose-related and consistent throughout the dosage interval. Accumulation indices of exposure from treatment cycles 1 to 2 were 1.64 (17.5%) in the 60 µg/kg dose group and 1.46 (17.5%) in the 80 µg/kg dose group.
Results showed that at the ≥60 µg/kg dose, the overall response rate reported with the ADC was 31.7% (n = 13/41). Notably, no responses were reported below the 60 µg/kg dose.
Additionally, treatment-emergent adverse events (TEAEs) were experienced by 95.5% of patients (n = 42/44). Among the most common toxicities reported were diarrhea (25.0%), fatigue (25.0%), pyrexia (25.0%), and reduced platelet count (20.5%). Eight immune-associated TEAEs were observed in 7 patients and included grade 1 swelling face and peripheral neuropathy (both n = 1); grade 2 erythema multiforme (n = 1), hypothyroidism (n = 1), hyperthyroidism (n = 2); and grade 3 dermatitis exfoliative and thyroiditis (both n = 1). Thirteen patients with NHL discontinued treatment because of TEAEs.
The ADC continues to be evaluated in this trial as well as in a phase 1b clinical trial in solid tumors (NCT03621982).