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Priority Review of Belantamab Mafodotin for R/R Multiple Myeloma

The FDA granted a priority review for a Biologics License Application (BLA) seeking approval of belantamab mafodotin for the treatment of patients with relapsed or refractory multiple myeloma whose prior therapy included an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.

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The BLA is based on data from the pivotal DREAMM-2 (DRiving Excellence in Approaches to Multiple Myeloma) study, recently published in The Lancet Oncology, which enrolled heavily pre-treated patients who had actively progressing multiple myeloma that had worsened despite current standard of care (2019;


The study focused on the immunoconjugate targeting B-cell maturation antigen (BCMA) in a heavily pre-treated patient population who was refractory to an immunomodulatory drug and a proteasome inhibitor, and refractory or intolerant to an anti-CD38 antibody. Belantamab mafodotin has the potential to be the first anti-BCMA treatment available to patients.


In 2017, belantamab mafodotin was granted Breakthrough Therapy designation by the FDA, which is intended to facilitate the development of investigational medicines that have shown clinical promise for conditions where there is significant unmet need.


Belantamab mafodotin is an investigational immunoconjugate comprising a humanized anti-B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker.


The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway has been shown to be important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients and BCMA membrane expression is universally detected in myeloma cell lines (Clin Cancer Res 2013;19(8):2048-2060).


Avapritinib for Gastrointestinal Stromal Tumor With a Rare Mutation

The FDA approved avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including D842V mutations. It is the first therapy approved for patients with GIST harboring a PDGFRA exon 18 mutation.


Efficacy was investigated in NAVIGATOR (NCT02508532), a multi-center, single-arm, open-label trial enrolling 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with PDGFRA D842V mutations. The trial initially enrolled patients at a starting dose of 400 mg orally once daily, which was later reduced to the recommended dose of 300 mg orally once daily due to toxicity. Patients received avapritinib until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate (ORR) based on disease assessment by independent radiological review using modified RECIST 1.1 criteria. An additional efficacy outcome measure was response duration.


For patients harboring a PDGFRA exon 18 mutation, the ORR was 84 percent (95% CI: 69%, 93%), with 7 percent complete responses and 77 percent partial responses. For the subgroup of patients with PDGFRA D842V mutations, the ORR was 89 percent (95% CI: 75%, 97%), with 8 percent complete responses and 82 percent partial responses. The median response duration was not reached with a median duration of follow-up for all patients of 10.6 months (range 0.3-24.9 months); 61 percent of the responding patients with exon 18 mutations had a response lasting 6 months or longer (31% of patients with an ongoing response were followed for less than 6 months).


The most common adverse reactions (incidence >= 20%) in patients who received avapritinib were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness.


The recommended avapritinib dose is 300 mg orally once daily on an empty stomach, at least 1 hour before and 2 hours after a meal.


Tazemetostat for Advanced Epithelioid Sarcoma

The FDA granted accelerated approval to tazemetostat for adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.


Efficacy was investigated in a single-arm cohort (cohort 5) of a multi-center trial (Study EZH-202, NCT02601950) in patients with histologically confirmed, metastatic, or locally advanced epithelioid sarcoma. Patients were required to have INI1 loss, detected using local tests, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received tazemetostat 800 mg orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were confirmed overall response rate (ORR) according to RECIST v1.1 (assessed by blinded independent central review) and duration of response.


The ORR for the 62 patients in cohort 5 was 15 percent (95% CI: 7%, 26%), with 1.6 percent having complete responses and 13 percent partial responses; 67 percent of those responding had responses lasting 6 months or longer.


The most common adverse reactions (incidence >=20%) were pain, fatigue, nausea, decreased appetite, vomiting, and constipation. The recommended tazemetostat dose is 800 mg taken orally twice daily with or without food.