Ygalo Continues to Induce Clinically Meaningful Responses in Relapsed or Refractory Multiple Myeloma, Phase 1/2 Trials Show

Ygalo (melflufen) combination therapy continues to lead to clinically meaningful responses, without significant side effects, in patients with relapsed or refractory multiple myeloma, updated data from Phase 1/2 trials show.

The new findings were presented in two posters, titled “ANCHOR (OP-104): A Phase 1 study update of melflufen and dexamethasone plus bortezomib or daratumumab in relapsed/refractory multiple myeloma patients refractory to an IMiD or a proteasome inhibitor,” and “O-12-M1: An evaluation of time to next treatment in melflufen and dexamethasone-treated patients with relapsed/refractory multiple myeloma,” at the 24th Congress of the European Hematology Association, June 13–16, 2019, in Amsterdam.

Ygalo is a lipophilic peptide-conjugated alkylator developed by Oncopeptides that works by rapidly delivering a cancer-killing agent (an alkylating peptide) to malignant myeloma cells.

The medication is intended to work as a therapy for triple refractory patients with multiple myeloma — patients who received and failed to respond to treatment with at least one immunomodulatory drug (IMiD), one proteasome inhibitor, and one anti-CD38 monoclonal antibody.

During the meeting, the company presented updated data from two ongoing Phase 1/2 clinical trials — ANCHOR (NCT03481556) and O-12-M1 (NCT01897714) — assessing the safety and efficacy of Ygalo in combination with other agents for the treatment of relapsed or refractory myeloma patients.

In the O-12-M1 study, the safety and efficacy of Ygalo in combination with dexamethasone was tested in a group of 45 patients who had received at least two prior therapies.

At the time of data cut-off, treatment with Ygalo and dexamethasone led to disease stabilization in 76% of the patients. The median time to next treatment — the start of treatment until the next treatment (or to the patient’s death, whichever happened first) — was 7.9 months. Patients lived for a median of 20.7 months.

“The results from the O-12-M1 study demonstrate that melflufen can offer disease stabilization and favourable time to the next treatment. It is strategically important from a health economic perspective and supports the potential that melflufen may play an important role in the treatment of patients with RRMM [relapsed or refractory multiple myeloma],” Jakob Lindberg, CEO of Oncopeptides, said in a press release.

In the ANCHOR study, the safety and efficacy of Ygalo in combination with dexamethasone and Velcade (bortezomib) or Darzalex (daratumumab) was tested in a group of patients who had received one to four previous therapies and failed to respond to treatment with an IMiD, a proteasome inhibitor, or both.

At the time of data cut-off, five patients had been treated with the triple combination of Ygalo, dexamethasone, and Velcade (regimen A; three with Ygalo at 30 mg and two with Ygalo at 40 mg); while 24 patients had been treated with the triple combination of Ygalo, dexamethasone, and Darzalex (regimen B; six with Ygalo at 30 mg and 18 with Ygalo at 40 mg).

The median treatment duration was 7.4 months for those treated with regimen A, and 7.9 and 1.2 months for those treated with regimen B, receiving Ygalo at a dose of 30 mg and 40 mg, respectively.

In regimen A, one patient stopped treatment due to disease progression after receiving 10 months of therapy. In regimen B, none of the patients receiving Ygalo at a dose of 30 mg stopped treatment so far, and two of those receiving Ygalo at a dose of 40 mg had to discontinue treatment on the recommendation of their physicians.

Among those who completed two or more treatment cycles, the overall response rate was 100% for those in regimen A and 82% for those in regimen B. Treatment responses improved with continued therapy in patients from both groups.

Both triple combinations were considered safe and well-tolerated by patients. No dose-limiting toxicities were found in any of the groups over the course of the trial, and severe or life-threatening adverse events were easily manageable, including mostly blood abnormalities (e.g. low white blood cell count and platelet levels).

“It is very encouraging to see consistently high response rates with deepening responses over time for melflufen in combination with proteasome inhibition and anti-CD38 therapies in the ongoing ANCHOR study in patients with relapsed/refractory multiple myeloma,” Lindberg commented. 

“The progression free survival similarly looks encouraging with some patients having been on treatment for more than a year and at this point in time only one patient in each arm has experienced disease progression. Together with the emerging safety and tolerability profile, this strengthens our belief that melflufen could add value for myeloma patients also as part of combination regimens,” he added.