FDA Lifts Partial Clinical Hold on Pivotal Phase 2 Trial of Camidanlumab Tesirine

July 6, 2020

The FDA lifted the partial clinical hold on the on the pivotal phase 2 trial of camidanlumab tesirine (Cami) – designed to evaluate the antibody drug conjugate in patients with relapsed or refractory Hodgkin lymphoma.

The FDA lifted the partial clinical hold on the on the pivotal phase 2 trial of camidanlumab tesirine (Cami) – designed to evaluate the antibody drug conjugate (ADC) in patients with relapsed or refractory Hodgkin lymphoma, according to ADC Therapeutics.

The trial is intended to support the company’s biologics license application for Cami to be submitted to the FDA.

The safety and efficacy of Cami, formerly known as ADCT-301, will continue to be evaluated in the 100-patient, multicenter, open-label, single-arm clinical trial. To be eligible to enroll in the trial, patients must have pathologically confirmed relapsed or refractory Hodgkin lymphoma, and have failed 3 prior lines of therapy, including brentuximab vedotin (Adcetris) and a checkpoint inhibitor approved for Hodgkin lymphoma, such as nivolumab (Opdivo) or pembrolizumab (Keytruda).

“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 Cami,” Jay Feingold, MD, PhD, senior vice president and chief medical officer of ADC Therapeutics, said in a press release. “During the partial clinical hold we continued to treat patients benefiting from Cami, and now look forward to resuming the enrollment of new patients in the trial as soon as possible.”

Cami is an ADC containing a monoclonal antibody that binds to CD25 that conjugates, or becomes temporarily united in order to exchange genetic material, to the pyrrolobenzodiazepine (PBD) dimer payload, tesirine, which gives molecules that can cross-link DNA – which leads to a substantial increase in potency and DNA binding affinity and an extension of sequence-selectivity compared with monomers.

“Once bound to a CD25-expressing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead killing the cell with an immunogenic cell death,” the release explained. “The intra-tumoral release of its PBD warhead may also cause bystander killing of neighboring tumor cells. The ADC also depletes CD25-positive regulatory T cells in the tumor environment. All of these properties of Cami may enhance immune-mediated anti-tumor activity.”

Cami is also being evaluated in a phase 1a/1b clinical trial in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma and a phase 1b clinical trial in solid tumors.

Reference:

ADC Therapeutics. ADC Therapeutics Announces U.S. Food and Drug Administration Has Lifted Partial Clinical Hold on Pivotal Phase 2 Clinical Trial of Camidanlumab Tesirine. Published July 6, 2020. https://ir.adctherapeutics.com/press-releases/press-release-details/2020/ADC-Therapeutics-Announces-US-Food-and-Drug-Administration-Has-Lifted-Partial-Clinical-Hold-on-Pivotal-Phase-2-Clinical-Trial-of-Camidanlumab-Tesirine/default.aspx. Accessed July 6, 2020.