Confirmatory Phase 3 Trial Needed Prior to Camidanlumab Tesirine BLA Submission for Accelerated Approval Path, FDA Says

For camidanlumab tesirine to be considered for an accelerated approval path in relapsed/refractory Hodgkin lymphoma, the FDA has strongly recommended conducting confirmatory phase 3 research at the time of biologic license application submission.

Although camidanlumab tesirine has demonstrated promising efficacy in a phase 2 trial (NCT04052997) for relapsed/refractory Hodgkin lymphoma, the FDA has strongly recommended conducting a randomized confirmatory phase 3 trial, preferably with full enrollment, at the time of biologic license application (BLA) submission, according to a press release from developer ADC Therapeutics.1

Due to this, the BLA submission for camidanlumab tesirine will be delayed, with full clinical enrollment on the phase 3 trial estimated to take at least 2 years. ADC Therapeutics intends to work in conjunction with the FDA on recommended actions and perusing the best regulatory path moving forward.

Updated safety and efficacy findings from the single-arm phase 2 clinical trial for camidanlumab tesirine in patients with relapsed/refractory classical Hodgkin lymphoma highlighted an overall response rate of 70.1% (n = 82/117; 95% CI, 60.9%-78.2%) and a complete response (CR) rate of 33.3% (n = 39).2 After a median follow-up of 10.7 months (range, 1.2-25.2+), the median duration of response was 13.7 months (95% CI, 7.4-14.7) for the total population, 14.5 months (95% CI, 7.4-not reached [NR]) for complete responders, and 7.9 months (95% CI, 3.8-NR) for patients with a partial response. Moreover, median progression-free survival was 9.1 months (95% CI, 5.1-15.0).2

Camidanlumab tesirine is an antibody-drug conjugate consisting of a human IgG1 anti-CD25 monoclonal antibody conjugated to SG3199, a pyrrolobenzodiazepine dimer cytotoxin. It was administered to patients on the first day of every 3-week cycle during the multicenter, open-label trial at a dose of 45 μg/kg on day 1 of every 3-week cycle for the first 2 cycles and was reduced to 30 μg/kg thereafter.

The trial included patients with relapsed or refractory classical Hodgkin lymphoma who had received at least 3 previous lines of systemic therapy or at least 2 lines if ineligible for hematopoietic stem cell transplantation­. Other inclusion criteria included an ECOG performance status of 0 to 2 as well as adequate organ function according to prespecified acceptable screening laboratory values.

Patients were excluded if they had prior therapy with the study agent or any post-transplantation lymphoproliferative disorders. Other exclusion criteria included having any active second primary malignancy aside from non-melanoma skin cancers, non-metastatic prostate cancer, cervical cancer in-situ, ductal or lobular carcinoma in situ of the breast, or another malignancy judged not to be exclusionary by the company’s medical monitor and an investigator.

ADC Therapeutics also stated that, although a phase 1b study assessing camidanlumab tesirine in combination with pembrolizumab (Keytruda) in solid tumors (NCT03621982) demonstrated promising immunomodulatory activity, the signals were not significant enough to move forward with the study.

References

  1. ADC Therapeutics reports third quarter 2022 financial results and provides business updates. News Release. ADC Therapeutics. November 8, 2022. Accessed November 10, 2022. https://bit.ly/3A37QRn
  2. Carlo-Stella C, Ansell S, Zinzani PL, et al. HL-339 camidanlumab tesirine: updated efficacy and safety in an open-label, multicenter, phase 2 study of patients with relapsed or refractory classical hodgkin lymphoma (R/R cHL). Clin Lymphoma Myeloma Leuk. 2022;22(suppl 2):S347. doi:10.1016/S2152-2650(22)01478-1