Updated findings from phase 3 APOLLO show an improvement in progression-free survival with daratumumabe plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone alone.
Subcutaneous daratumumab (Darzalex) in combination with pomalidomide (Pomalyst) and dexamethasone demonstrated an improvement in progression-free survival (PFS) compared with pomalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma who have previously been treated with lenalidomide (Revlimid) and a proteasome inhibitor (PI), according to topline findings from the phase 3 APOLLO (MMY3013; NCT03180736) trial announced by Genmab in a press release.1
The safety profile for the combination with subcutaneous daratumumab was also found to be consistent with that of individual therapies.
Data from the APOLLO trial will be reviewed with health authorities in preparation for future regulatory submissions for the combination. Additionally, results from the trial will be presented at an upcoming medical meeting.
“We are pleased with these positive results for daratumumab, administered as a subcutaneous formulation, in combination with pomalidomide and dexamethasone. The corresponding intravenous regimen was previously approved by the US FDA based on the phase 1 single-arm EQUULEUS study,” said Jan van de Winkel, PhD, CEO of Genmab, in the press release.
In June 2017, the FDA approved the combination of intravenous daratumumab, pomalidomide, and dexamethasone for the treatment of patients with multiple myeloma who have received at least 2 prior treatments, including lenalidomide and a PI, based on data from the phase 1 EQUULEUS (MMY1001) trial. The APOLLO study was meant to confirm the results of the EQUULEUS study.
EQUULEUS included 103 patients who had relapsed/refractory multiple myeloma, had received a median of 4 prior therapies (range, 1-13), and were refractory to their last treatment. Patients received intravenous daratumumab 16 mg/kg plus pomalidomide 4 mg per day for 21 days of a 28-day cycle and weekly 40-mg dexamethasone.2
The primary end point was safety and secondary end points were overall response rate (ORR) and minimal residual disease (MRD).
The ORR was 60% and was 58% among double-refractory patients. Twenty-nine percent of patients who achieved a complete response or better achieved MRD negativity at a rate of 10-5. The median duration of response was not estimable (NE).
The median PFS was 8.8 months (95% CI, 4.6-15.4) and the median overall survival was 17.5 months (95% CI, 13.3-NE). At 1 year, the estimated survival rate was 66% (95% CI, 55.6%-74.8%).
Frequent grade ≥3 adverse events included neutropenia (78%), anemia (28%), and leukopenia (24%). Also, infusion-related reactions were observed in 50% and a higher incidence of neutropenia was reported, both due to daratumumab treatment.
APOLLO is a randomized, open-label, multicenter phase 3 trial that included a 1:1 randomization of about 302 patients to either the daratumumab arm or pomalidomide and dexamethasone alone. The trial originally began patients on intravenous daratumumab, but once a subcutaneous formulation of daratumumab with recombinant human hyaluronidase was approved, patients were allowed to switch over to the subcutaneous form.
In the experimental arm, daratumumab was administered intravenously at 16 mg/kg or subcutaneously at 1800 mg weekly for 8 weeks, then every 2 weeks for 16 weeks, and then every 4 weeks thereafter until disease progression or unacceptable toxicity.
Secondary end points included ORR, very good partial response or better rate, complete response or better rate, MRD negativity rate, time to response, duration of response, time to next therapy, overall survival, safety, patient-reported outcomes, and pharmacokinetics.
Patients with prior exposure to an anti-CD38 monoclonal antibody or pomalidomide, previous allogeneic stem cell transplant or recent autologous stem cell transplantation, other recent malignancy, meningeal involvement, chronic obstructive pulmonary disease, significant cardiac disease, active hepatitis, known HIV, gastrointestinal disease, on ongoing toxicities were excluded from the trial.
1. Genmab Announces European Myeloma Network and Janssen Achieve Positive Topline Results from Phase 3 APOLLO Study of Daratumumab in Combination with Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma. News release. Genmab A/S. July 31, 2020. Accessed August 1, 2020. https://bit.ly/3fkdWPW
2. Chari A, Suvannasankha A, Fay JW, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017;130(8):974-981. doi:10.1182/blood-2017-05-785246