The FDA has approved tebentafusp-tebn (Kimmtrak – Immunocore), a first-in-class bispecific gp100 peptide-HLA-directed CD3 T-cell engager, for treatment of HLA-A*02:01-positive unresectable or metastatic uveal melanoma in adults.

The FDA has approved tislelizumab (Tevimbra – BeiGene), a programmed death receptor-1 (PD-1) blocking antibody, for treatment of unresectable or metastatic esophageal squamous cell cancer in adults who received prior systemic chemotherapy that did not include a programmed death ligand-1 (PD-L1) inhibitor.

Lifileucel (Amtagvi – Iovance), a tumor-derived autologous T-cell immunotherapy, has received accelerated approval from the FDA for one-time treatment of adults with unresectable or metastatic melanoma previously treated with a programmed death receptor-1 (PD-1) inhibitor, and if BRAF V600 mutation-positive, a BRAF inhibitor with or without a mitogen-activated kinase (MEK) inhibitor. It is the first cellular therapy to be approved for use in solid tumors. Accelerated approval of lifileucel was based on objective response rates.

Opdualag (BMS), a fixed-dose combination of two immune checkpoint inhibitors — nivolumab (Opdivo), a programmed death receptor-1 (PD-1) inhibitor, and relatlimab-rmbw, a lymphocyte-activation gene-3 (LAG-3) blocking antibody — has been approved by the FDA for treatment of unresectable or metastatic melanoma in patients ≥12 years old. Relatlimab, which is only available in combination with nivolumab, is the first LAG-3 blocking antibody to become available in the US. Immune checkpoint inhibitors, including the anti-CTLA-4 antibody ipilimumab (Yervoy) and the PD-1 inhibitors nivolumab and pembrolizumab (Keytruda), have been available for several years for treatment of melanoma.

The FDA has approved the mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor cobimetinib (Cotellic – Genentech) for use in combination with the BRAF kinase inhibitor vemurafenib (Zelboraf) for treatment of unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.

The FDA has approved the combined use of the programmed death receptor-1 (PD-1) blocking antibody nivolumab (Opdivo) and the anti-CLA-4 antibody ipilimumab (Yervoy) for treatment of BRAF V600 wild-type unresectable or metastatic melanoma. This is the first immunotherapy combination to be approved for treatment of any type of cancer.

After our article on nivolumab (Opdivo – BMS) for treatment of metastatic melanoma and metastatic squamous non-small cell lung cancer (NSCLC) was published in the most recent issue of The Medical Letter (June 8, 2015),1 some new data became available supporting the efficacy of the drug in previously untreated melanoma and previously treated nonsquamous NSCLC.

MELANOMA – In a double-blind trial, 945 patients with previously untreated, unresectable stage III or IV melanoma were randomized to receive ipilimumab, nivolumab, or combination therapy with ipilimumab and nivolumab. Progression-free survival, a primary endpoint, improved by 43% with nivolumab (median 6.9 months) and by 58% with combination therapy (median 11.5 months), compared to ipilimumab (median 2.9 months). In patients with tumors that expressed the programmed death ligand 1 (PD-L1) on ≥5% of cells, median progression-free survival was similar in the nivolumab and combination groups (both 14.0 months); in those with tumors that expressed PD-L1 on <5% of cells, it was 5.3 months with nivolumab alone and 11.2 months with both drugs. Rates of complete or partial response were 19.0% with ipilimumab, 43.7% with nivolumab, and 57.6% with combination therapy. At least one severe (grade 3-4) drug-related adverse effect occurred in 27.3% of patients receiving ipilimumab, 16.3% of those receiving nivolumab, and 55.0% of those receiving both drugs.2

NONSQUAMOUS NSCLC – In an open-label trial (available only as an abstract), 582 patients with advanced nonsquamous NSCLC that had progressed during or after treatment with a platinum doublet-based regimen (and, if appropriate, a kinase inhibitor) were randomized to receive nivolumab or docetaxel until disease progression or unacceptable toxicity occurred. Nivolumab significantly improved overall survival, the primary endpoint, by 27% compared to docetaxel (median 12.2 vs 9.4 months). Survival rates in the two groups were similar in patients with tumors expressing PD-L1 on <1% of cells, but in patients with tumors expressing PD-L1 on ≥1%, ≥5%, and ≥10% of cells, nivolumab improved overall survival by 41%, 57%, and 60%, respectively, compared to docetaxel. Patients receiving nivolumab were significantly more likely to have an objective response (19.2% vs 12.4%). Severe (grade 3+) drug-related adverse effects occurred in 10.5% of patients receiving nivolumab and in 53.7% of those receiving docetaxel.3

1. Nivolumab (Opdivo) for metastatic melanoma and metastatic NSCLC. Med Lett Drugs Ther 2015; 57:85.
2. J Larkin et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015 May 31 (epub).
3. L Paz-Ares et al. Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC). J Clin Oncol 2015; 33 (suppl; abstr LBA109). Available at: abstracts.asco.org. Accessed June 11, 2015.

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The FDA has approved nivolumab (Opdivo – BMS), an IV programmed death receptor-1 (PD-1) blocking antibody, for treatment of unresectable or metastatic melanoma that has progressed following treatment with ipilimumab (and a BRAF inhibitor in patients who are BRAF V600 mutation positive) and for treatment of metastatic squamous non-small cell lung cancer (NSCLC) that has progressed on or after platinum-based chemotherapy. It is the second PD-1 inhibitor to be marketed in the US after pembrolizumab (Keytruda), and the first to be approved for treatment of NSCLC.

The FDA has approved pembrolizumab (Keytruda – Merck), a human programmed death receptor-1 (PD-1) blocking antibody, for treatment of unresectable or metastatic melanoma that has progressed following treatment with ipilimumab (Yervoy) and, if the patient is BRAF V600 mutation positive, a BRAF inhibitor. It is the fi rst PD-1 inhibitor to be marketed in the US. Nivolumab, another PD-1 inhibitor, is available in Japan. Pembrolizumab was previously known as lambrolizumab.

The FDA has approved two new oral kinase inhibitors for treatment of unresectable or metastatic melanoma: dabrafenib (Tafinlar – GSK) for melanomas with BRAF V600E mutations and trametinib (Mekinist – GSK) for melanomas with either BRAF V600E or V600K mutations. Dabrafenib is not recommended for patients with wild-type BRAF (BRAF-negative) melanoma, and trametinib is not recommended for patients who have received prior BRAF-inhibitor therapy.

The FDA has approved vemurafenib (Zelboraf – Genentech), a kinase inhibitor, for treatment of unresectable or metastatic melanoma with the BRAF V600E mutation, which is found in 30-60% of melanomas. An FDA-approved test can detect the mutation in DNA from melanoma tissue.

The FDA has approved ipilimumab (Yervoy – Bristol-Myers Squibb), a recombinant human monoclonal antibody, for treatment of unresectable or metastatic melanoma.