C4 Therapeutics has reported positive results from the Phase I dose escalation stage of a Phase I/II clinical trial of its MonoDAC IKZF1/3 degrader, CFT7455, to treat multiple myeloma (MM) and non-Hodgkin’s lymphomas (NHL).

The three-arm Phase I portion is designed to analyse the safety profile of the therapy, as well as the maximum tolerated dose and anti-tumour activity, in relapsed/refractory (r/r) MM and R/R NHL patients.

A concluded arm analysed CFT7455 as a single agent in R/R MM patients while the other two arms are currently assessing CFT7455 plus dexamethasone in R/R MM patients, and CFT7455 monotherapy in NHL patients, respectively. 

The newly reported data comprises findings from the first section of CFT7455 as a single agent, and interim results from CFT7455 plus dexamethasone in r/r MM patients.

Findings showed that daily treatment with CFT7455 monotherapy led to deep degradation of IKZF1/3.

CFT7455 was well tolerated, with neutropenia, anaemia, and leukopenia observed to be the most frequently reported adverse events (AEs) of Grade 3 or above.

After day 14, a decrease in CFT7455 plasma concentrations was observed, with the recovery of degraded proteins by day 28, facilitating neutrophil recovery.

The highest dose of 75µg per day was given to four subjects, with one subject reporting partial response (PR) while all attained stable disease (SD) or better.

CFT7455 elicited CD8+ T-cell activation by boosting the effector memory T-cell subset, as needed for adaptive immunity.

In addition, CFT7455 plus dexamethasone has, so far, been found to be well tolerated in R/R MM patients.

C4 Therapeutics chief medical officer Len Reyno said: “We are excited CFT7455 monotherapy is showing promising signs of anti-myeloma and immunomodulatory activity, and anti-myeloma activity when combined with dexamethasone, particularly in patients who have undergone numerous lines of prior therapy for multiple myeloma, including BCMA therapies.

“We have established 14 days on/14 days off as the optimal dosing schedule, which is consistent with our preclinical data supporting CFT7455 as a rationally designed IKZF1/3 degrader, with the potential to offer a new therapy for patients with r/r multiple myeloma.”