Over the past year (January to December 2020), the U.S. Food and Drug Administration (FDA) granted approval to several novel drugs and new indications for older therapeutic agents used in oncology and hematology. A brief review of new approvals appears here. For complete prescribing information for any of these agents, visit www.accessdata.fda.gov/scripts/cder/daf.

Pralsetinib

On December 1, the FDA approved pralsetinib (Gavreto) for adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy or RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine–refractory.

On September 4, pralsetinib was granted accelerated approval for adult patients with metastatic RET fusion–positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test.

Both pralsetinib approvals were based on findings from the open-label, multicenter, multicohort ARROW clinical trial (ClinicalTrials.gov identifier NCT03037385).

Naxitamab

On November 25, naxitamab (Danyelz) was approved in combination with granulocyte-macrophage colony-stimulating factor for pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy. Approval was based on findings from two single-arm, open-label trials: Study 201 (NCT03363373) and Study 12-230 (NCT01757626).

Pembrolizumab

On November 13, accelerated approval was granted to pembrolizumab (Keytruda) 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. Approval was based on findings from KEYNOTE-355 (NCT02819518), a multicenter, double-blind, randomized, placebo-controlled trial.

On October 14, approval was extended for pembrolizumab for adult patients with relapsed or refractory classical Hodgkin lymphoma (HL) and pediatric patients with refractory classical HL or classical HL that has relapsed after two or more lines of therapy. Approval in this setting was based on findings from KEYNOTE-204 (NCT02684292), a phase III, randomized, open-label trial.

On June 29, pembrolizumab was approved for the first-line treatment of patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer. This approval was based on findings from KEYNOTE-177 (NCT02563002), a multicenter, international, open-label, active-controlled, randomized trial.

On June 24, pembrolizumab was approved for patients with recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation. Approval was based on findings from the multicenter, multicohort, nonrandomized, open-label KEYNOTE-629 trial (NCT03284424).

On June 16, accelerated approval was granted to pembrolizumab for adult and pediatric patients with unresectable or metastatic tumor mutational burden-high [≥ 10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and no satisfactory alternative treatment options. Approval was based on a multicenter, nonrandomized, open-label trial, KEYNOTE-158 (NCT02628067).

On April 28, accelerated approval was granted to a new dosing regimen of 400 mg every 6 weeks for pembrolizumab across all currently approved adult indications, in addition to the current 200 mg every-3-weeks dosing regimen. This approval was based on cohort B of KEYNOTE-555 (NCT03665597), an international, single-arm, multicenter study.

Venetoclax

On October 16, approval was granted to venetoclax (Venclexta) in combination with azacitidine, decitabine, or low-dose cytarabine for untreated acute myeloid leukemia (AML). Approval was based on findings from two randomized, double-blind, placebo-controlled trials: VIALE-A (NCT02993523) and VIALE-C (NCT03069352).

Nivolumab/Ipilimumab and Nivolumab Alone

On October 2, nivolumab (Opdivo) plus ipilimumab (Yervoy) was approved as first-line treatment for adult patients with unresectable malignant pleural mesothelioma. Approval was based on findings from CheckMate 743 (NCT02899299), a randomized, open-label trial.

On June 10, nivolumab monotherapy was approved for patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based chemotherapy. Approval was based on ATTRACTION-3 (NCT02569242), a multicenter, randomized, active-controlled, open-label trial.

On May 26, nivolumab plus ipilimumab and two cycles of platinum-doublet chemotherapy was approved as first-line treatment of patients with metastatic or recurrent NSCLC, with no EGFR or ALK genomic tumor aberrations. Approval in this setting was based on CheckMate 9LA (NCT03215706), a randomized, open-label trial.

On May 15, the combination of nivolumab plus ipilimumab was approved as first-line treatment for patients with metastatic NSCLC whose tumors express PD-L1 (≥ 1%), as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. This approval was based on CheckMate 227 (NCT02477826), a randomized, open-label, multipart trial.

On March 10, accelerated approval was granted to the combination of nivolumab and ipilimumab for patients with hepatocellular carcinoma who have been previously treated with sorafenib. Approval was based on cohort 4 of CheckMate 040 (NCT01658878) a multicenter, multicohort, open-label trial.

Azacitidine

On September 1, azacitidine tablets (Onureg) were approved for continued treatment of patients with AML who achieved first complete remission or complete remission with incomplete blood cell count recovery following intensive induction chemotherapy and who are not able to complete intensive curative therapy. This oral form of azacitidine should not be substituted for intravenous or subcutaneous formulations, which have different indications and dosing regimens. Approval was based on findings from QUAZAR (NCT01757535), a multicenter, randomized, double-blind, placebo-controlled trial.

Daratumumab Combinations

On August 20, carfilzomib (Kyprolis) and daratumumab (Darzalex) in combination with dexamethasone was approved for adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. Approval was based on findings from ­CANDOR (NCT03158688), a randomized, open-label, multicenter trial.

On May 1, a fixed combination of daratumumab and hyaluronidase-fihj (Darzalex Faspro) was approved for adult patients with newly diagnosed or relapsed/refractory multiple myeloma. Approval was based on COLUMBA (NCT03277105), an open-label noninferiority trial.

Belantamab Mafodotin-blmf

On August 5, belantamab mafodotin-blmf (Blenrep) was approved for adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Approval was based on findings from DREAMM-2 (NCT 03525678), an open-label, multicenter trial.

Tafasitamab-cxix

On July 31, accelerated approval was granted to 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. Accelerated approval was based on findings from L-MIND (NCT02399085), an open-label, multicenter, single-arm trial.

Atezolizumab Combinations and Monotherapy

On July 30, atezolizumab (Tecentriq) was approved in combination with cobimetinib and vemurafenib for patients with BRAF V600 mutation–positive unresectable or metastatic melanoma. Approval was based on findings from a double-blind, randomized, placebo-controlled, multicenter trial (IMspire150, NCT02908672).

On May 29, atezolizumab in combination with bevacizumab (Avastin) was approved for patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy. Approval was based on IMbrave150 (NCT03434379), a multicenter, international, open-label, randomized trial.

On May 18, atezolizumab monotherapy was approved for the first-line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression or PD-L1–stained tumor-infiltrating immune cells covering at least 10% of the tumor area, with no EGFR or ALK genomic tumor aberrations. Approval was based on IMpower110 (NCT02409342), a multicenter, international, randomized, open-label trial.

Brexucabtagene Autoleucel

On July 24, accelerated approval was granted to brexucabtagene autoleucel (Tecartus), a CD19-directed genetically modified autologous T-cell immunotherapy, for adult patients with relapsed or refractory mantle cell lymphoma. Approval was based findings from ZUMA-2 (NCT02601313), an open-label, multicenter, single-arm trial.

Decitabine/Cedazuridine

On July 7, an oral combination of decitabine and cedazuridine (Inqovi) was approved for adult patients with myelodysplastic syndrome. Approval was based on findings from two open-label, randomized, crossover trials: ASTX727-01-B (NCT02103478) and ASTX727-02 (NCT03306264).

Avelumab

On June 30, avelumab (Bavencio) was approved for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. Approval was based findings from JAVELIN Bladder 100 (NCT02603432), a randomized, multicenter, open-label trial.

Pertuzumab/Trastuzumab/Hyaluronidase-zzxf

On June 29, a new fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) was approved. Approval was based on findings from FeDeriCa (NCT03493854), an open-label, multicenter, randomized trial.

Sacituzumab Govitecan-hziy

On April 22, accelerated approval was granted to sacituzumab govitecan-hziy (Trodelvy) for adult patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease. Approval was based on IMMU-132-01 (NCT 01631552), a multicenter, single-arm trial.

Selinexor

On June 22, accelerated approval was granted to selinexor (Xpovio) for adult patients with relapsed or refractory diffuse DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma (FL), after at least two lines of systemic therapy. Approval was based on findings from SADAL (KCP-330-009; NCT02227251), a multicenter, single-arm, open-label trial.

Tazemetostat

On June 18, accelerated approval was granted to tazemetostat (Tazverik), an EZH2 inhibitor, for adult patients with relapsed or refractory FL whose tumors are positive for an EZH2 mutation, as detected by an FDA-approved test, and who have received at least two prior systemic therapies. It also was approved for adult patients with relapsed or refractory FL who have no satisfactory alternative treatment options. Approval was based on two open-label, single-arm cohorts, cohort 4 (EZH2-mutated FL) and cohort 5 (EZH2 wild-type FL), of a multicenter trial (Study E7438-G000-101, NCT01897571).

Tucatinib/Trastuzumab/Capecitabine

On April 17, tucatinib (Tukysa) was approved for use in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti–HER2-based regimens in the metastatic setting. Approval was based on the HER2CLIMB trial (NCT02614794).

Neratinib/Capecitabine

On February 25, neratinib (Nerlynx) in combination with capecitabine was approved for treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2–based regimens in the metastatic setting. Approval was based on NALA (NCT01808573), a randomized, multicenter, open-label clinical trial.

Gemtuzumab Ozogamicin

On June 16, the indication of gemtuzumab ozogamicin (Mylotarg) was extended for newly diagnosed CD33-positive AML to include pediatric patients 1 month and older. The extension was based on AAML0531 (NCT00372593), a multicenter randomized study.

Lurbinectedin

On June 15, accelerated approval was granted to lurbinectedin (Zepzelca) for adult patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. Approval was based on the PM1183-B-005-14 trial (Study B-005; NCT02454972), a multicenter open-label, multicohort study.

Ramucirumab/Erlotinib

On May 29, ramucirumab (Cyramza) in combination with erlotinib was approved for first-line treatment of metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations. Approval was based on RELAY (NCT02411448), a multinational, randomized, double-blind, placebo-controlled, multicenter study.

Brigatinib

On May 22, brigatinib (Alunbrig) was approved for adult patients with ALK-positive metastatic NSCLC, as detected by an FDA-approved test. Approval was based on ALTA 1L (NCT02737501), a randomized, open-label, multicenter trial.

Olaparib

On May 19, olaparib (Lynparza) was approved for adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer, who have had disease progression following prior treatment with enzalutamide or abiraterone. Approval was based on PROfound (NCT02987543), an open-label, multicenter trial.

Ripretinib

On May 15, ripretinib (Qinlock) was approved for adult patients with advanced gastrointestinal stromal tumor who have received prior treatment with three or more kinase inhibitors, including imatinib. Approval was based on INVICTUS (NCT03353753), an international, multicenter, randomized, double-blind, placebo-controlled trial.

Rucaparib

On May 15, rucaparib (Rubraca) was approved 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. Approval was based on TRITON2 (NCT02952534), an ongoing, multicenter, single-arm clinical trial.

Pomalidomide

On May 14, the indication of pomalidomide (Pomalyst) was expanded to include treating adult patients with AIDS-related Kaposi sarcoma after failure of highly active antiretroviral therapy and Kaposi sarcoma in adult patients who are HIV-negative. The expansion was based on Study 12-C-0047, an open-label, single-arm clinical trial.

Olaparib/Bevacizumab

On May 8, the indication of olaparib was expanded to include its combination with bevacizumab 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. The expansion was based on PAOLA-1 (NCT03737643), a randomized, double-blind, placebo-controlled, multicenter trial.

Selpercatinib

On May 8, accelerated approval was granted to selpercatinib (Retevmo) for the following indications: adult patients with metastatic RET fusion–positive NSCLC; adult and pediatric patients at least 12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy; and adult and pediatric patients at least 12 years of age with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine–refractory. Accelerated approval was based on the multicenter, open-label, multicohort clinical trial LIBRETTO-001.

Capmatinib

On May 6, accelerated approval was granted to 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. Accelerated approval was based on the GEOMETRY mono-1 trial (NCT02414139), a multicenter, nonrandomized, open-label, multicohort study.

Niraparib

On April 29, niraparib (Zejula) was approved 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. Approval was based on PRIMA (NCT02655016), a double-blind, placebo-controlled trial.

Ibrutinib/Rituximab

On April 21, the indication of ibrutinib (Imbruvica) was expanded to include its combination with rituximab for the initial treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Approval was based on the E1912 trial (NCT02048813), a randomized, multicenter, open-label, actively controlled trial.

Pemigatinib

On April 20, accelerated approval was granted to pemigatinib (Pemazyre) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement, as detected by an FDA-approved test. Approval was based on FIGHT-202 (NCT02924376), a multicenter, open-label, single-arm trial.

Mitomycin

On April 15, a pyelocaliceal formulation of mitomycin (Jelmyto) was approved for adult patients with low-grade upper tract urothelial cancer. Approval was based on OLYMPUS (NCT02793128), an ongoing, single-arm, multicenter trial.

Selumetinib

On April 10, selumetinib (Koselugo) was approved for pediatric patients, 2 years of age and older, with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Approval was based on SPRINT (NCT01362803), a National Cancer Institute–sponsored, open-label, multicenter, single-arm trial.

Encorafenib/Cetuximab

On April 8, encorafenib (Braftovi) in combination with cetuximab was approved 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. Approval was based on a randomized, active-controlled, open-label, multicenter trial (BEACON CRC, NCT02928224).

Luspatercept-aamt

On April 3, luspatercept-aamt (Reblozyl) was approved for the treatment of patients with anemia that failed to respond to an erythropoiesis-stimulating agent and required two or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ringed sideroblasts or with myelodysplastic/myeloproliferative neoplasm with ringed sideroblasts and thrombocytosis. Approval was based on the MEDALIST trial (NCT02631070), a randomized, multicenter, double-blind, placebo-controlled trial.

Durvalumab/Etoposide Plus a Platinum Agent

On March 27, durvalumab (Imfinzi) in combination with etoposide and either carboplatin or cisplatin was approved as first-line treatment of patients with extensive-stage small cell lung cancer. Approval was based on CASPIAN, a randomized, multicenter, active-controlled, open-label, trial (NCT03043872).

Isatuximab-irfc/Pomalidomide/Dexamethasone

On March 2, isatuximab-irfc (Sarclisa) in combination with pomalidomide and dexamethasone was approved for adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. Approval was based on ICARIA-MM (NCT02990338), a multicenter, multinational, randomized, open-label, two-arm, phase III study.