FDA Lifts Partial Clinical Hold on Camidanlumab Tesirine R/R Hodgkin Lymphoma Trial

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).

References

  1. ADC Therapeutics announces US Food and Drug Administration has lifted partial clinical hold on pivotal phase 2 clinical trials of camidanlumab tesirine. News release. ADC Therapeutics. July 6, 2020. Accessed July 6, 2020. bit.ly/2VPbbzg.
  2. Study to evaluate the efficacy and safety of camidanlumab tesirine (ADCT-301) in patients with relapsed/refractory Hodgkin lymphoma. ClinicalTrials.gov. Updated April 7, 2020. Accessed July 6, 2020. https://clinicaltrials.gov/ct2/show/NCT04052997.
  3. Collins GP, Horwitz SM, Davies A, et al. ADCT-301 (camidanlumab tesirine), a novel pyrrolobenzodiazepine-based CD25-targeting antibody drug conjugate, in a phase 1 study of relapsed/refractory non-Hodgkin lymphoma shows activity in T-cell lymphoma. Blood. 2018;132(suppl 1):1658. doi:10.1182/blood-2018-99-115986