2020 Approvals Expand Access to Care for Patients Across Tumor Types

February 4, 2021

Pipeline Report | <b>Pipeline Report: January 2021</b>

In a year marked by collaboration and innovation, therapeutic developments in oncology care once again dominated the novel drug approvals in 2020.

In a year marked by collaboration and innovation, therapeutic developments in oncology care once again dominated the novel drug approvals in 2020. In total, 21 novel agents were approved across hematology/ oncology, including 3 diagnostic imaging agents for the treatment of patients with breast cancer, prostate cancer, and neuroendocrine tumors, respectively. Additionally, new formulations and expanded indications and biosimilar approvals across tumor types opened up the accessibility of agents for patient populations, including reduced time in the clinic.

Such approvals included subcutaneous daratumumab (Darzalex) plus hyaluronidase-fihj (Darzalex Faspro), which reduces the administration time from hours for intravenous daratumumab to minutes for patients with multiple myeloma. Additionally, the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) was approved, providing an outpatient treatment option patients with HER2-positive breast cancer. Further, the approval of the novel oral formulation of decitabine and cedazuridine (Inqovi), marked the first nonintravenous treatment for patients with myelodysplastic syndromes (MDS).1,2

The year 2020 was a decidedly promising one for patients with lung cancer, in particular those with nonsmall cell lung cancer (NSCLC). Specifically, the FDA approved 3 novel agents for patients with NSCLC and expanded the indication of 6 other agents. Two agents, selpercatinib (Retevmo) and pralsetinib (Gavreto), were approved for patients harboring RET mutations and for patients with indications that include medullary thyroid cancer (MTC).1

Approvals in other rare cancers also shared the spotlight in 2020, including those for gastrointestinal stromal tumors (GIST), a malignancy that affects the walls of the digestive system. The first, avapritinib (Ayvakit), joined 3 other targeted agents for the treatment of patients with this disease. The second, ripretinib (Qinlock), became the first agent approved in the fourth line for those patients who have exhausted all approved treatment options.1,2

The 21 novel agents approved across hematology/ oncology, in chronological order, are the following:

  • Avapritinib (Ayvakit) for adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including D842V mutations;
  • Tazemetostat (Tazverik) for adults and pediatric patients 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection;
  • Isatuximab-irfc (Sarclisa) in combination with pomalidomide (Pomalyst) and dexamethasone for adult patients with multiple myeloma who have received at least 2 prior therapies, including lenalidomide (Revlimid) and a proteasome inhibitor;
  • Selumetinib (Koselugo) for pediatric patients 2 years and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas;
  • Tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and capecitabine for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received 1 or more prior anti-HER2–based regimens in the metastatic setting;
  • Pemigatinib (Pemazyre) for the treatment of adults with previously treated, unresectable, locally advanced, or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement, as detected by an FDA-approved test;
  • Sacituzumab govitecan-hziy (Trodelvy) for adult patients with metastatic triple-negative breast cancer who received at least 2 prior therapies for metastatic disease;
  • Capmatinib (Tabrecta) for adult patients with metastatic NSCLC whose tumors have a mutation that leads to MET exon 14 skipping, as detected by an FDA-approved test;
  • Selpercatinib (Retevmo) for 3 indications: adult patients with metastatic RET fusion–positive NSCLC, adults and pediatric patients at least 12 years of age with advanced or metastatic RET-mutant MTC who require systemic therapy, and adults and pediatric patients at least 12 years of age with advanced or metastatic RET fusion–positive thyroid cancer that has stopped responding to radioactive iodine therapy or is not appropriate for radioactive iodine therapy;
  • Ripretinib (Qinlock) for adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib (Gleevec);
  • Fluoroestradiol F 18 (Cerianna) for the visual detection of estrogen receptor–positive lesions on positron emission tomography (PET) scan images in addition to tissue biopsy in patients with recurrent or metastatic breast cancer;
  • Lurbinectedin (Zepzelca) for adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy;
  • Decitabine plus cedazuridine (Inqovi), an oral combination for adult patients with MDS including previously treated and untreated de novo and secondary MDS with French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups;
  • Tafasitamab-cxix (Monjuvi), a CD19-directed cytolytic antibody, indicated in combination with lenalidomide for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, and who are not eligible for autologous stem cell transplant;
  • Belantamab mafodotin-blmf (Blenrep) for adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies, including an antiCD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent;
  • Copper Cu 64 dotatate (Detectnet) injection for the detection of somatostatin receptor–positive neuroendocrine tumors in adults;
  • Pralsetinib (Gavreto) for adult patients with meta-static RET fusion–positive NSCLC as detected by an FDA-approved test;
  • Naxitamab-gqgk (Danyelza) in combination with granulocyte-macrophage colony-stimulating factor for pediatric patients 1 year and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a partial or minor response to or stable disease with prior therapy;
  • Gallium 68 PSMA-11, a radioactive diagnostic agent that is administered in the form of an intravenous injection for PET imaging of prostate-specific membrane antigen–positive lesions in men with suspected prostate cancer metastasis who are potentially curable by surgery or radiation therapy and with suspected prostate cancer recurrence based on elevated serum prostate-specific antigen levels;
  • Margetuximab-cmkb (Margenza) in combination with chemotherapy for the treatment of adult patients with metastatic HER2-positive breast cancer who have received 2 or more prior anti-HER2 regimens, at least 1 of which was for metastatic disease; and
  • Relugolix (Orgovyx), the first oral gonadotropin-releasing hormone receptor antagonist for adult patients with advanced prostate cancer.

New Indications

The FDA granted approval for the following indications:

  • Pembrolizumab (Keytruda) for patients with BCG-unresponsive, high-risk, non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy;
  • Neratinib (Nerlynx) in combination with capecitabine for adult patients with advanced or metastatic HER2-positive breast cancer who have received 2 or more prior anti-HER2–based regimens in the metastatic setting;
  • Nivolumab (Opdivo) plus ipilimumab (Yervoy) for patients with hepatocellular carcinoma who have been previously treated with sorafenib (Nexavar);
  • Durvalumab (Imfinzi) in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage SCLC;
  • Luspatercept-aamt (Reblozyl) for the treatment of patients with anemia that failed to respond to an erythropoiesis-stimulating agent and required 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk MDS with ringed sideroblasts or with myelodysplastic/myeloproliferative neoplasm with ringed sideroblasts and thrombocytosis;
  • Encorafenib (Braftovi) in combination with cetuximab (Erbitux) for the treatment of adult patients with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy;
  • Mitomycin gel (Jelmyto) for adult patients with low-grade upper tract urothelial cancer;
  • Ibrutinib (Imbruvica) in combination with rituximab (Rituxan) for the initial treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma;
  • Niraparib (Zejula) for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who achieved a complete or partial response to first-line platinum-based chemotherapy;
  • Daratumumab plus hyaluronidase-fihj (Darzalex Faspro) for adult patients with newly diagnosed or relapsed/refractory multiple myeloma;
  • Olaparib (Lynparza) in combination with bevacizumab (Avastin) for first-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency–positive status, defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability;
  • Pomalidomide (Pomalyst) for adult patients with AIDS-related Kaposi sarcoma after failure of highly active antiretroviral therapy and Kaposi sarcoma in adult patients who are HIV negative;
  • Rucaparib (Rubraca) for patients with deleterious BRCA mutation (germline and/or somatic)–associated metastatic castration-resistant prostate cancer who have been treated with androgen receptor–directed therapy and a taxane-based chemotherapy;
  • Nivolumab plus ipilimumab as first-line treatment for patients with metastatic NSCLC whose tumors express PD-L1 at least 1%, as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations;
  • Atezolizumab (Tecentriq) for the first-line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 stained ≥ 50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥ 10% of the tumor area), with no EGFR or ALK genomic tumor aberrations;
  • Olaparib for adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer who have progressed following prior treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga);
  • Brigatinib (Alunbrig) for adult patients with ALK-positive metastatic NSCLC as detected by an FDA-approved test;
  • Nivolumab plus ipilimumab and 2 cycles of platinum-doublet chemotherapy as first-line treatment for patients with metastatic or recurrent NSCLC with no EGFR or anaplastic ALK genomic tumor aberrations;
  • Atezolizumab plus bevacizumab for patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy;
  • Ramucirumab (Cyramza) in combination with erlotinib (Tarceva) for first-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 mutations;
  • Nivolumab for patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum- based chemotherapy;
  • Gemtuzumab ozogamicin (Mylotarg) for newly diagnosed CD33+ acute myeloid leukemia in pediatric patients 1 month and older;
  • Pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden–high (≥ 10 mutations per megabase) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options;
  • Tazemetostat for adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies, and for adult patients who have no satisfactory alternative treatment options;
  • Selinexor (Xpovio) for adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy;
  • Pembrolizumab for patients with recurrent or meta-static cutaneous squamous cell carcinoma that is not curable by surgery or radiation;
  • Fixed-dose combination of pertuzumab (Perjeta), trastuzumab, and hyaluronidase-zzxf (Phesgo) for subcutaneous injection in combination with chemotherapy for the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either > 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer; in combination with chemotherapy for the adjuvant treatment of HER2-positive early breast cancer at high risk of recurrence; and in combination with docetaxel for patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemo-therapy for metastatic disease;
  • Pembrolizumab for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high or mismatch repair–deficient colorectal cancer;
  • Avelumab (Bavencio) for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy;
  • Atezolizumab in combination with cobimetinib (Cotellic) and vemurafenib (Zelboraf) for patients with BRAF V600 mutation–positive unresectable or meta-static melanoma;
  • Carfilzomib (Kyprolis) and daratumumab (Darzalex) in combination with dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 lines of therapy;
  • Azacitidine tablets (Onureg) for continued treatment of patients with acute myeloid leukemia who achieved first complete remission or complete remission with incomplete blood count recovery follwing intensive induction chemotherapy and are not able to complete intensive curative therapy;
  • Nivolumab plus ipilimumab as first-line treatment for adult patients with unresectable malignant pleural mesothelioma;
  • Pembrolizumab for adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) and pediatric patients with refractory cHL or cHL that has relapsed after 2 or more lines of therapy;
  • Venetoclax (Venclexta) in combination with azacitidine, decitabine, or low-dose cytarabine for newly diagnosed acute myeloid leukemia in adults 75 years or older or who have comorbidities precluding intensive induction chemotherapy;
  • Pembrolizumab in combination with chemotherapy for the treatment of patients with locally recurrent, unresectable, or metastatic triple-negative breast cancer whose tumors express PD-L1 (combined positive score, ≥ 10) as determined by an FDA approved test;
  • Pralsetinib for adults and pediatric patients 12 years and older with advanced or metastatic RET-mutant MTC who require systemic therapy or RET fusion–positive thyroid cancer who require systemic therapy and who are refractory to radioactive iodine (if radioactive iodine is appropriate);
  • Selinexor in combination with bortezomib (Velcade) and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 prior therapy; and
  • Osimertinib (Tagrisso) for adjuvant therapy after tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations.

Cell Therapy

Brexucabtagene autoleucel (Tecartus), a CD19-directed genetically modified autologous T-cell immunotherapy, was approved for the treatment of adult patients with relapsed or refractory mantle cell lymphoma.

Biosimilars

  • Pegfilgrastim-apgf (Nyvepria) was approved as a biosimilar to the reference product pegfilgrastim (Neulasta) and is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.3
  • Rituximab-arrx (Riabni) was approved as a biosimilar to the reference product rituximab and is indicated for the treatment of adult patients with non-Hodgkin lymphoma (NHL), specifically those with relapsed or refractory, low-grade or follicular, CD20+ B-cell NHL as a single agent; previously untreated follicular, CD20+, B-cell NHL in combination with first-line chemotherapy and in patients achieving a complete or partial response to a rituximab product in combination with chemo-therapy, as single-agent maintenance therapy; nonprogressing (including stable disease), low-grade, CD20+, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy; previously untreated diffuse large B-cell, CD20+ NHL in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone or other anthracycline-based chemotherapy regimens. It also is approved for adults with previously untreated and treated CD20+ CLL in combination with fludarabine and cyclophosphamide; and for granulomatosis with polyangiitis and microscopic polyangiitis in adult patients in combination with glucocorticoids.

References

1. Novel drug approvals for 2020. FDA. Updated January 13, 2021. Accessed January 17, 2021. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2020 

2. Hematology/oncology (cancer) approvals & safety notifications. FDA. Updated January 15, 2021. Accessed January 17, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/hematologyoncology-cancer-approvals-safety-notifications 

3. Biosimilar product information. FDA. Updated December 17, 2020. Accessed January 17, 2021. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information 

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