An update on the phase 3 OCEAN study of melflufen in relapsed/refractory multiple myeloma reported that patients stayed on treatment longer than had been previously estimated.
An update on the phase 3 OCEAN study of melflufen in relapsed/refractory multiple myeloma reported that patients stayed on treatment longer than had been previously estimated, according to Oncopeptides AB, the developer of the first-in-class anticancer peptide-drug conjugate.1
As a result, the company announced that topline results from the trial will read out in the first half of 2021 instead of later this year, as previously reported.
"A recent analysis indicates that patients enrolled in the OCEAN-study continue treatment for a longer period of time than originally estimated, which speaks to the potential benefit patients can have by participating in this trial," Jakob Lindberg, CEO of Oncopeptides, stated in a press release. "However, this most likely increases the time required to reach the number of disease progression events needed to complete the study. We will continue patient enrollment to enable an analysis of results within a reasonable timeframe."
The open-label, randomized phase 3 OCEAN trial (NCT03151811) is comparing melflufen plus dexamethasone to pomalidomide (Pomalyst) plus dexamethasone in patients with relapsed/refractory multiple myeloma who are refractory to lenalidomide (Revlimid).
Oncopeptides is planning to submit a new drug application (NDA) to the FDA seeking accelerated approval for melflufen for the treatment of patients with relapsed/refractory myeloma. The NDA will be based on findings from the phase 2 HORIZON trial, in which melflufen in combination with dexamethasone induced a 26% overall response rate (ORR) in patients with triple-class refractory multiple myeloma.2
Triple-class refractory is defined as the patient being refractory to immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies.
The phase 2 HORIZON trial (OP-106) included 157 patients with relapsed/refractory multiple myeloma who had received ≥2 prior lines of therapy, been exposed to an IMiD and PI, and were refractory to pomalidomide (Pomalyst) and/or daratumumab (Darzalex). The trial population included patients who were triple-class refractory and/or had extramedullary disease (EMD) and/or had cytogenetic high-risk features.
Patients received 40 mg of melflufen on day 1 of each 28-day cycle along with 40 mg of dexamethasone weekly (20 mg for patients aged ≥75 years). Treatment was administered until progressive disease or unacceptable toxicity. ORR was the primary endpoint, with secondary outcome measures including clinical benefit rate, progression-free survival (PFS), overall survival (OS), duration of response, and safety. The cutoff date for the final analysis was January 14, 2020.
At the final analysis, the ORR in the overall ITT population (n = 157) was 30% by independent review committee (IRC) assessment and 29% by investigator assessment. The ORR in the triple-class refractory group (n = 119) was 26% by both IRC and investigator review, and the ORR in the EMD group (n = 55) was 27% and 24%, respectively. There were also 2 unconfirmed responders at the data cutoff who were subsequently confirmed. When factoring these patients in, the ITT ORR was 31% and the triple-class refractory ORR was 27% by both IRC and investigator review.
There were no new safety signals at the final analysis. Oncopeptides plans to report the full results in a peer-reviewed publication.
The final findings reported by Oncopeptides showed an increased ORR in the triple-class refractory population from the data reported from the HORIZON trial at the 2019 ASH Annual Meeting.3 At this earlier analysis, the triple-class refractory cohort included 97 patients and the ORR was 24%. The median PFS in this group was 4 months, the median OS was 11.3 months, and the median duration of response was 7.5 months.
The ITT population in the analysis shared at ASH included 125 patients who had received a median of 5 prior lines of therapy. Ninety-seven percent of patients were refractory to their last line of treatment, 71% were triple-class refractory, and 32% had EMD. The ITT ORR was 29% and the clinical benefit rate was 37%.
Among patients with EMD (n = 42), the ORR was 24%, the median PFS was 3 months, the median OS was 8.1 months, and the median duration of response was 5.1 months.
Regarding toxicity, grade 3/4 adverse events were mainly hematologic, and the occurrence of nonhematologic AEs was infrequent.
Oncopeptides intends to submit a supplemental NDA to the FDA once the results from the OCEAN trial are available.