Current landscape of FDA approval requests and trial updates in multiple myeloma

The Multiple Myeloma (MM) Hub are pleased to report on the current status of awaited U.S. Food & Drug Administration (FDA) approvals in MM, as well as provide a trial update from ICARIA-MM.

Selinexor: FDA priority review status

In October 2018, the FDA granted priority review for selinexor, a first-in-class, oral exportin 1 (XPO1) inhibitor. A meeting of the oncologic drugs advisory committee (ODAC) is scheduled for tomorrow, 26 February, 2019. The hearing will discuss the combination of selinexor and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) who have received at least three prior therapies and are refractory to at least one proteasome inhibitor (PI), one immunomodulatory drug (IMiD) and an anti-CD38 monoclonal antibody.¹

The ODAC briefing document is available and the draft voting question for the committee centres around whether approval of selinexor should be postponed until the randomized phase III trial (BOSTON) results are available.² The MM Hub will report on the results of this priority review once published.

Background²

The application is based on part 2 of the STORM study (KCP-330-012) which was a multicentre, open-label, single arm, phase IIb trial investigating the efficacy and safety of treatment with selinexor (80mg orally, twice weekly) and dexamethasone (20mg orally twice weekly) in 123 enrolled patients.

• Efficacy (N = 122)
  • Overall response rate: 25.4% (95% CI, 18.0–34.1)
  • Median duration of response in responders (N = 31): 4.4 months (0.8–9.0)
• Safety (N = 123)
  • Mortality within 30 days of treatment: N = 23
  • Causes of mortality: disease progression (N = 13), fatal treatment-emergent adverse events (TEAE; N = 10)
  • TEAE any grade: 100%
  • TEAE grade ≥3: 93.5%
  • TEAE was the cause of study discontinuation in 28.5% of patients

FDA approval requested for daratumumab in combination with lenalidomide and dexamethasone for patients with newly diagnosed MM (NDMM)

The FDA has been asked to approve daratumumab in combination with lenalidomide and dexamethasone (DRd) as first-line treatment for patients with NDMM, who are ineligible for stem cell transplant and high dose chemotherapy, based on the results of the MAIA phase III trial (NCT02252172).³

Background

This request is following the results of the MAIA trial, reported during the American Society of Hematology (ASH) 60^th Annual Meeting and Exposition, previously covered by the MM Hub.⁴ Daratumumab is an anti-CD38 monoclonal antibody, already authorized in other MM indications. The MAIA study randomized 737 patients with NDMM, non-eligible for stem cell transplant to DRd (N = 368) or Rd (N = 369). There was a 44% reduction in the risk of disease progression or death in the DRd group. A complete response or better was achieved in 48% of patients receiving DRd versus 25% in the Rd group.

Isatuximab: phase III trial ICARIA-MM meets its primary endpoint

The phase III ICARIA-MM trial (NCT02990338) recently met its primary endpoint of improving progression free survival (PFS) in patients with RRMM. The study investigated the use of isatuximab with pomalidomide and dexamethasone compared to pomalidomide and dexamethasone alone. The results are expected to be published during an upcoming medical meeting and the drug company responsible for the trial will use these results later in the year for regulatory submissions.⁵

Background

ICARIA-MM is a multi-center, open-label, phase III trial investigating the addition of isatuximab to the two-drug regimen of pomalidomide and dexamethasone in 307 patients who were randomized. Eligible patients had received two or more prior therapies, including at least 2 cycles of lenalidomide and a PI. Isatuximab was administered intravenously (10 mg/kg) with pomalidomide and dexamethasone until disease progression or unacceptable toxicity.⁵