Ygalo Continues to Show Promising Activity in Relapsed, Refractory Multiple Myeloma

Ygalo (melflufen) combination therapy continues to demonstrate promising results, without significant side effects, in patients with relapsed or refractory multiple myeloma, updated data from two clinical trials show.

The findings were presented at the Society of Hematologic Oncology (SOHO) 2019 Annual Meeting, held Sept. 11–14 in Houston, Texas.

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 clinical trials — the HORIZON Phase 2 trial (NCT02963493), and the ANCHOR Phase 1/2 trial (NCT03481556) — assessing the safety and effectiveness of Ygalo in combination with other agents for treating relapsed or refractory myeloma patients.

In an oral presentation titled, “HORIZON (OP-106) Study of Melflufen in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Refractory to Daratumumab and/or Pomalidomide: Updated Efficacy and Safety,” Christopher Maisel, MD, one of the trial’s investigators, presented interim data from HORIZON that had been announced initially at the European Hematology Association (EHA) 2019 Annual Congress, held June 13-16 in Amsterdam, Netherlands.

In HORIZON, the safety and effectiveness of Ygalo in combination with dexamethasone is being tested in multiple myeloma patients who had received at least two prior therapies, including one IMiD and one proteasome inhibitor, and failed to respond to treatment with Darzalex (daratumumab) and/or Pomalyst (pomalidomide).

All patients received Ygalo intravenously at a dose of 40 mg on day 1 and 40 mg of dexamethasone on days 8, 15 and 22 in cycles of 28 days, until disease progression or unacceptable toxicity.

The trial’s primary goal was to assess overall response rate (the percentage of patients who responded to treatment). Secondary goals included overall survival, progression-free survival (the time patients lived until disease progression or death), and duration of response.

Oncopeptides is planning to enroll up to 150 patients into HORIZON. As of May 6, 121 patients had already been dosed, including 108 who had completed two cycles of treatment. Interim data from the trial presented at the meeting has shown that:

• The proportion of patients responding partially or completely to treatment was 28%, and a total of 40% achieved at least minor responses to treatment;
• Patients lived for a median of 11.2 months and remained alive and without signs of disease worsening for a median of 4.0 months; the median duration of response was 4.4 months;
• In most patients (86%), Ygalo and dexamethasone led to disease stabilization or better;
• Treatment was considered safe and well-tolerated;
• Treatment-related serious adverse effects occurred in 20% of the study participants and included fever caused by low neutrophil levels (5%) and low platelet counts (2%).

These findings, as well as the detailed design of HORIZON and patient characteristics, also were shared in a poster presentation during the September meeting.

“These interim data from the HORIZON clinical trial demonstrate the potential for melflufen to be a novel therapeutic option for patients with RRMM [relapse or refractory multiple myeloma],” Maisel said in a press release. Maisel is with  Texas Oncology and Baylor Sammons Cancer Center in Dallas, Texas.  “I am encouraged by these results, and glad to see that there is a selective alkylator with efficacy and manageable toxicity in RRMM patients, as this patient population remains a significant unmet need.”

Oncopeptides is planning to use data from HORIZON to support the submission of a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) requesting the accelerated approval of Ygalo for the treatment of triple-refractory myeloma patients. The company expects to file the application in early 2020.

“The selection of these data for oral presentation at the esteemed SOHO 2019 Annual Meeting reinforce the scientific rigor of Oncopeptides’ clinical development program supporting our lead candidate melflufen, and we are excited about this first presentation of these interim data to U.S. clinician audiences,” said Jakob Lindberg, CEO of Oncopeptides. “As we look toward our planned NDA submission in the first quarter of 2020, we look forward to providing continuing updates on the HORIZON clinical trial at additional upcoming medical congresses.”

In another poster titled, “ANCHOR (OP-104) Study of Melflufen and Dexamethasone Plus Bortezomib or Daratumumab in Patients With Relapsed/Refractory Multiple Myeloma (RRMM) Refractory to an IMiD and/or a Proteasome Inhibitor (PI): Phase 1 Update,” the company presented updated data from the ANCHOR trial.

In ANCHOR, the safety and effectiveness of Ygalo in combination with dexamethasone and Velcade (bortezomib) or Darzalex (daratumumab) were 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 (May 8), 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).

New findings presented at the meeting showed both combinations were safe and well-tolerated by patients. Evolving efficacy also was promising in both combination therapies, with all patients responding to regimen A and 82% responding to regimen B. Currently, most patients (90%) are still receiving treatment.

The trial is still recruiting patients to the group receiving Ygalo at a dose of 40 mg.

The safety and effectiveness of Ygalo in combination with dexamethasone, or with Pomalyst and dexamethasone, for treating myeloma patients who had received between two and four prior therapies and failed to respond to treatment with Revlimid (lenalidomide) are currently being evaluated in the ongoing OCEAN Phase 2 trial (NCT03151811).