Phase 1b Trial of ADCT-301 in Advanced Solid Tumors Doses First Patient

Phase 1b Trial of ADCT-301 in Advanced Solid Tumors Doses First Patient

A Phase 1b clinical trial of ADCT-301 (camidanlumab tesirine) in adult patients with locally advanced or metastatic solid tumors has dosed the first patient.

Patient enrollment for this multicenter, open-label study (NCT03621982) is ongoing. Approximately 50 patients will be recruited. (Information about study locations and contacts available here.)

To be included, a patient needs to have either head and neck, non-small cell lung cancer, gastric and esophageal cancers, pancreatic, bladder, renal cell carcinoma, melanoma, triple negative breast cancer, or ovarian cancer. Eligible patients also must be refractory (resistant) or intolerant to existing therapies and have adequate organ function.

ADCT-301, being developed by ADC Therapeutics, belongs to a type of therapy called antibody drug conjugates (ADCs). It is composed of an antibody that binds to a cell surface molecule known as CD25, linked to a pyrrolobenzodiazepine-based toxin.

CD25 is found in a subset of immune T-cells called regulatory T-cells, or Tregs, which infiltrate the local tumor’s environment. CD25 over-expression has been shown in both Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). When bound to CD25, ADCT-301 enters the cell with subsequent release of the toxin. This may kill neighboring tumor cells and induce immunogenic cell death, boosting the immune response against tumor cells.

The Phase 1b study intends to assess the safety, tolerability, pharmacokinetics (the compound’s absorption, distribution, metabolism and excretion in the body) and anti-tumor activity of ADCT-301. The trial’s dose escalation part is designed to determine a safe and tolerated dose, as well as an ADCT-301 dosing schedule to be further assessed in the dose expansion part of the study.

Treatment with ADCT-301 also is being assessed in a Phase 1a/1b trial in patients with relapsed and refractory HL and NHL (NCT02432235). Patient recruitment is underway in the U.S. and U.K.

Preliminary results presented at the 2018 American Society of Hematology (ASH) Annual Meeting revealed that, in HL patients with a median of five previous lines of therapy and no further approved therapeutic options, the overall response rate with ADCT-3101 was 86.5%. This included a 43% complete response rate — the disappearance of all signs of cancer — at the dose being considered for a Phase 2 study anticipated to start in 2019.

“We continue to be very encouraged by the anti-tumor activity of ADCT-301 in Hodgkin lymphoma and non-Hodgkin lymphoma,” Jay Feingold, MD, PhD, ADC’s chief medical officer and senior vice president of clinical development, said in a press release.

In turn, at the Society for Immunotherapy of Cancer’s (SITC) 33rd Annual Meeting, the Switzerland-based company revealed that a single dose of an engineered version of ADCT-301 had strong anti-tumor activity both as a stand-alone therapy and in combination with a checkpoint inhibitor in diverse solid tumor models with infiltrating CD25-positive Tregs.

Also, “re-challenged mice did not develop new tumors indicating the CD25-targeted ADC was able to induce tumor-specific protective immunity,” added Patrick van Berkel, PhD, ADC’s senior vice president of research and development.

Overall, “based on the immune-oncology potential ADCT-301 has demonstrated in preclinical studies,” Feingold said, “we are excited to be starting this clinical trial for ADCT-301 in solid tumors to see if we can make an impact and improve patient outcomes in multiple difficult-to-treat solid tumor cancers.”