FDA Approvals for Cancer Management in the First Quarter of 2022

In Quarter 1 of 2022, the FDA approved seven new indications for cancer management, with March being a near-record month with five approvals:

  • New PSMA-Targeted Radioligand Therapy for Metastatic Castration-Resistant Prostate Cancer. Approval was granted to lutetium (Lu)-177 vipivotide tetraxetan (Pluvicto™, Advanced Accelerator Applications USA, Inc.) to treat adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated previously with at least one androgen receptor (AR) pathway inhibitor and one or two taxane-based chemotherapies. This approval was based on results from the phase III, multicenter, open-label VISION trial (n=831), which randomized patients with progressive, PSMA-positive mCRPC to receive best standard of care (BSoC) alone or Lu 177 vipivotide tetraxetan. Additionally, all patients received androgen deprivation therapy. Investigators observed a statistically significant improvement in median overall survival (OS; 15.3 vs. 11.3 months; hazard ratio [HR], 0.62; P < 0.001) and in median radiographic progression-free survival (rPFS; 8.7 vs. 3.4 months; HR, 0.4; P < 0.001). The FDA simultaneously approved a kit for the preparation of gallium Ga 68 gozetotide (Locametz®, Novartis AG), a radioactive diagnostic agent for positron emission tomography (PET) of PSMA-positive lesions, to be used for identifying patients appropriate for treatment with Lu 177 vipivotide tetraxetan.
  • Pembrolizumab for MSI-H/dMMR Advanced Endometrial Carcinoma. Approval was given to pembrolizumab (Keytruda®, Merck), as a single agent for patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation. MSI-H or dMMR status must be determined by an FDA-approved test. Approval was based on efficacy results from a multicenter, non-randomized, open-label trial, KEYNOTE-158, which included patients with previously treated advanced MSI-H/dMMR tumors, including 90 patients with endometrial cancer (Cohorts D and K). The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR) as assessed by blinded independent central review (BICR). ORR was 46%; the median DoR was not reached, with 68% having a response duration of ≥12 months and 44% having a response duration of ≥24 months.
  • Dual LAG3 and PD-1 Checkpoint Inhibition for Unresectable or Metastatic Melanoma. The combination of nivolumab and relatlimab-rmbw (Opdualag™, Bristol Myers Squibb) was approved for adult and pediatric patients, 12 years or older, with unresectable or metastatic melanoma. This combo consists of a fixed dose of the LAG-3-blocking antibody relatlimab (160 mg) plus the programmed death receptor-1 (PD-1)-blocking antibody nivolumab (480 mg). Approval was based on RELATIVITY-047, a double-blinded, phase II–III trial in which 714 patients with previously untreated metastatic or unresectable stage III or IV melanoma were randomized to the nivolumab–relatlimab combo or nivolumab alone. The combination demonstrated a greater median PFS benefit (primary study endpoint) compared with nivolumab alone (10.1 vs. 4.6 months; HR, 0.75; P = 0.0055). OS was not statistically significant (HR, 0.80; P = 1.01), with median OS not reached in the combination arm and 34.1 months in the nivolumab arm.
  • Bispecific Fusion Protein Tebentafusp for Unresectable or Metastatic Uveal Melanoma. Approval was granted to tebentafusp-tebn (Kimmtrak®, Immunocore Limited), a bispecific gp100 peptide-HLA-directed CD3 T cell engager, for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma. This agent was approved based on efficacy results from IMCgp100-202, a randomized, phase III, open-label, multicenter trial of 378 patients with metastatic uveal melanoma. Patients were required to be HLA-A*02:01 genotype-positive, identified by a central assay. Patients with prior systemic therapy or localized liver-directed therapy were excluded; however, prior surgical resection of oligometastatic disease was permitted. Patients were randomized to receive tebentafusp or investigator’s choice of treatment of either pembrolizumab, ipilimumab, or dacarbazine. Treatment with tebentafusp resulted in longer OS than the investigator’s choice of therapy (21.7 vs. 16 months; HR, 0.51; P < 0.0001).
  • Adjuvant Olaparib for High-Risk Early Breast Cancer. The indication for olaparib (Lynparza®, AstraZeneca) in breast cancer was extended for use in the adjuvant setting for patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative, high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Clinicians must use an FDA-approved companion diagnostic for olaparib to select patients for treatment. This approval was based on the phase III, double-blind, placebo-controlled, international OlympiA trial in which 1836 patients with gBRCAm, HER2-negative, high-risk early breast cancer, who completed definitive local treatment and neoadjuvant or adjuvant chemotherapy (anthracycline/taxane-based), were randomized to receive 1 year of olaparib or placebo. OlympiA’s primary efficacy endpoint was invasive disease-free survival (IDFS). IDFS at 3 years was 86% for patients receiving olaparib and 77% for those receiving placebo (HR, 0.58; P < 0.0001). Furthermore, fewer deaths were reported with olaparib than with placebo (75 [8%] vs. 109 deaths [12%] and, as reported by the FDA, this difference was statistically significant (HR, 0.68; P = 0.0091).
  • Neoadjuvant Nivolumab Plus Platinum-Doublet for Early-Stage Lung Cancer. FDA-approved nivolumab (Opdivo®, Bristol Myers Squibb) in combination with platinum-doublet chemotherapy for patients with resectable non-small cell lung cancer (NSCLC) in the neoadjuvant setting. This is the first approved indication of neoadjuvant therapy in early-stage lung cancer. It was based on efficacy results from a phase III, open-label CHECKMATE-816 trial, in which 358 patients with resectable, histologically confirmed stage IB (≥4 cm)-IIIA NSCLC were randomly assigned to receive either nivolumab plus platinum-doublet chemotherapy or platinum chemotherapy alone. Patients were enrolled regardless of the tumor PD-L1 status. The primary endpoints were event-free survival (EFS) and pathologic complete response (pCR) by BICR. Median EFS was 31.6 months in the nivolumab plus chemotherapy arm and 20.8 months for those receiving chemotherapy alone (HR, 0.63; P = 0.0052). The pCR rate was 24% in the nivolumab plus chemotherapy arm and 2.2% in the chemotherapy-only arm.
  • New CAR T-cell Therapy for Relapsed or Refractory Multiple Myeloma. Approval was granted for the B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (CARVYKTI™, Janssen Biotech, Inc.) for the treatment of patients with relapsed or refractory multiple myeloma (MM) after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody. This approval was based on safety and efficacy results from a phase Ib/II, open label, multicenter CARTITUDE-1 study, evaluating ciltacabtagene autoleucel in 97 patients with relapsed or refractory, heavily pretreated MM; 82% had received four or more antimyeloma therapies. The primary efficacy endpoints were ORR and DoR, assessed by independent review committee using international response criteria for MM. The ORR was 97.9%, and among the 95 patients who responded, the median DoR was 21.8 months with a median follow up of 18 months. The prescribing information includes a boxed warning for cytokine-release syndrome (CRS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), immune effector cell-associated neurotoxicity syndrome (ICANS), parkinsonism and Guillain-Barré syndrome and their associated complications, and prolonged and/or recurrent cytopenia, all of which can be fatal or life-threatening. This treatment can be given only in specially certified hospitals.