In-depth inventory: 10 anti-tumor innovative drugs approved by the FDA in 2019

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In 2019, the FDA’s Center for Drug Evaluation and Research (CDER) approved many new drugs as usual.The approval of new drug therapies has improved the quality of life for many patients.For cancer patients, the new drug brings hope of survival and dignity.Throughout 2019, CDER approved a total of 48 innovative drugs, including 10 tumor-related drugs (excluding vaccines, sensitization products, blood and blood products, plasma derivatives, cells and gene therapy products or 2019 biological product evaluation and evaluationOther products approved by the research center).Next, we will retrospectively review these 10 innovative drugs according to the approved time: 1. Enhertu (fam-trastuzumab deruxtecan-nxki) drug summary Fam-trastuzumab deruxtecan-nxki is an antibody-conjugated drug (ADC), which is anA novel HER2-targeted antibody-cytotoxic drug coupling agent, a humanized HER2 monoclonal antibody trastuzumab coupled to a new topoisomerase I inhibitor camptothecin derivative via a peptidyl linker (DX-8951 derivative DXd).FDA-approved indication: for the treatment of adult patients with HER2-positive unresectable or metastatic breast cancer who have previously received two or more anti-HER2 therapies.Related clinical studies: The DESTINY-Breast01 (NCT03248492) one-arm trial phase II clinical study recruited a total of 184 patients with HER2-positive breast cancer who were resistant to existing HER drugs, including T-DM1 from Roche ADC, and had an average of 6 before treatmentAn early stage therapy.Results: After using Fam-trastuzumab deruxtecan-nxki, an objective response rate (ORR) of 60.9% and a disease control rate (DCR) of 97.3% were achieved.Patients had a median duration of response (DOR) of 14.8 months and a median progression-free survival (PFS) of 16.4 months.Innovation: Targeting the latest version of HER-2 ADC, based on tumor response rate and DOR-related data, this indication has received accelerated FDA approval.2. Summary of PADCEV (enfortumab vedotin-ejfv) drug Enfortumab vedotin-ejfv is also ADC. The drug consists of a human IgG1 monoclonal antibody enfortumab targeting Nectin-4 and a cytotoxic agent MMAE (monomethyl auristatin E, singleMethyl auristatin E, a microtubule disrupting agent).Nectin-4 is a therapeutic target that is highly expressed in a variety of solid tumors, including urothelial carcinoma (UC).FDA Indication: For patients with locally advanced or metastatic UC (the most common type of bladder cancer), specifically: have previously been treated with a PD-1 / PD-L1 inhibitor and are on neoadjuvant / adjuvant therapy or inPatients who have received a platinum-based chemotherapy regimen for locally advanced or metastatic disease.Related clinical studies: Results from the first cohort of EV-201 (NCT03219333) Phase II clinical studies.This cohort included 125 patients with locally advanced or metastatic UC who had previously received platinum-containing chemotherapy and PD-1 / PD-L1 inhibitors. The efficacy and safety of Enfortumab vedotin-ejfv were evaluated.Results: After treatment with Enfortumab vedotin-ejfv, the ORR was 44% (55/125, 95% CI: 35.1-53.2), the complete response rate was 12% (15/125), and the DOR was 7.6 months (range: 0.95-11.3+).Innovation: The first ADC drug approved for UC, and the first drug approved for patients with locally advanced or metastatic UC who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.3. Brukinsa (zanubrutinib) drug summary. Zanubrutinib is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK).BTK is a member of the Tec family of tyrosine kinases and is expressed in B cells, macrophages and monocytes, but not in T cells.BTK plays a vital role in signaling through B-cell receptors (BCR) and fcγ receptors (fcγr) in B cells and myeloid cells.BTK is considered a potential target for the treatment of various diseases involving B cell and / or macrophage activation.FDA Indication: Used to treat adult mantle cell lymphoma (MCL) patients who have previously received at least one therapy.Related clinical studies: BGB-3111-206 (NCT03206970) Phase 2 clinical trial ORR is 84% ​​(95% CI: 74%, 91%), including 59% complete response (FDG-PET scan is required in this trial) And 24% partial remission.The median DOR of this trial was 19.5 months (95% CI: 16.6, NE), and the median follow-up time was 18.4 months.BGB-3111-AU-003 (NCT02343120) In the global Phase 1/2 clinical trial, the ORR was 84% ​​(95% CI: 67%, 95%), including 22% complete remission (FDG-PET scan in thisNot necessary in the trial) and 62% partial remission.The median DOR of this trial was 18.5 months (95% CI: 12.6, NE), and the median follow-up time was 18.8 months.Innovation: Zanubrutinib becomes a competitive drug for AbbVie / Johnson & Johnson’s BTK inhibitor Ibrutinib.4. ROZLYTREK (entrectinib) Entrotinib is a pan-TrkA / B / C, ROS1, and ALK inhibitor that is administered orally and has central nervous system activity.FDA approved indications: for the treatment of NTRK fusion-positive adults and children, patients with locally advanced or metastatic solid tumor progression or solid tumors without standard treatment after initial treatment, and patients with ROS1 positive non-small cell lung cancer (NSCLC).Related clinical studies: Phase II clinical trial STARTRK-2, phase I STARTRK-1, phase I ALKA-372-001, 53 patients with ROS1 activated gene fusion and 54 patients with locally advanced or metastatic NTRK fusion positive solid tumorsdata.In addition, data from the STARTRK-NG phase I / Ib study in pediatric patients was included in the NDA.Results: 1) In patients with NTRK fusion-positive solid tumors, the ORR (tumor shrinkage) of emtricinib (RXDX-101) was 57.4%, and objective responses were observed across 10 different types of tumors (tumorZoom out).In patients with brain metastases, emtratinib had an intracranial ORR of 54.5%, of which more than a quarter achieved complete remission (all lesions disappeared).2) In patients with locally advanced or metastatic ROS1-positive NSCLC, emtricinib has an ORR of 77.4% and a DOR of more than 2 years (24.6 months).These patients included 20 (37.7% of the total enrolled patients) untreated and treated patients with brain metastases, with a response rate of 55%.Innovation: The FDA approved the third “unlimited cancer” blockbuster anti-cancer therapy after Pabolizumab and larotrectinib.5. TURALIO (pexidartinib) drug summary Pexidartinib is a new oral small molecule that can effectively inhibit colony-stimulating factor-1 receptor (CSF1R).CSF1R is a major growth driver of abnormal cells in the synovium of TGCT.In addition, pexidatinib can also inhibit c-kit and FLT3-ITD, and several clinical studies are underway.FDA Indication: For the treatment of adult patients with symptomatic tendon sheath giant cell tumor (TGCT) who have functional limitations and are not suitable for surgery.TGCT is a rare tumor that affects the synovium and tendon sheath. The tumor is rarely malignant, but it can cause thickening or excessive growth of the synovium and tendon sheath, causing damage to surrounding tissues.Relevant clinical studies: Data from the pivotal phase III study ENLIVEN (NCT02371369) helped Pexidartinib be approved successfully.The ENLIVEN study enrolled 120 patients, 59 of whom received placebo. The primary efficacy endpoint was the total response rate (ORR) analyzed after 25 weeks of treatment.Results: At week 25 of treatment, the ORR of the oral Pexidartinib treatment group was 38% and the placebo group was 0%. The data were statistically significant (p <0.0001) and reached the study's main endpoint.In the Pexidartinib treatment group, the complete response rate was 15% and the partial response rate was 23%; the control group had zero data.Innovation: The first drug for a rare disease, tendon sheath giant cell tumor.6. Nubeqa (Darolutamide) drug profile Darolutamide is an androgen receptor inhibitor (ARi). Its unique chemical structure binds to the receptor with a strong affinity and has a strong antagonistic activity, thereby inhibiting the receptor function andGrowth of prostate cancer cells.Indication: The FDA is approved to treat patients with non-metastatic castration-resistant prostate cancer (nmCRPC).Approved based on the ARAMIS trial: a randomized (2: 1), double-blind, placebo-controlled, multicenter, phase III study to evaluate the efficacy and safety of darolutamide combined with androgen deprivation therapy (ADT) and placebo combined with ADT.Results: The primary efficacy endpoint, MFS, was significantly improved, with a median of 40.4 months and 18.4 months in the placebo plus ADT group (p <0.0001).Disease-related knowledge: 1. Castration-resistant prostate cancer (CRPC) Prostate cancer is the second most common male malignancy in the world.In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and approximately 358,000 people worldwide died of prostate cancer.Prostate cancer is the fifth leading cause of death from cancer in men.The prostate is part of the male reproductive system, and prostate cancer is caused by abnormal proliferation of cells in the prostate.It mainly affects men over 50 years of age, and the risk of disease increases with age.CRPC is a type of advanced disease that continues to progress even after ADT treatment and when testosterone in the body drops to very low levels.2. Therapeutic methods Common treatment methods include surgery, radiation therapy, and the use of hormone receptor antagonists, which prevent the formation of testosterone or prevent it from acting in the target location for treatment.However, in almost all cases, cancer eventually becomes resistant to hormone therapy.3. The study's metastasis-free survival time (MFS) defines the time from the time of randomization to the first evidence of distant metastasis or death of any cause confirmed by a blind independent center review within 33 weeks after the last assessment scan., Whichever occurs first.Swipe up and down to see all the content Innovation: For CRPC, significantly extend MFS.7. Xpovio (selinexor) drug overview Selinexor: the first, oral, selective nuclear export inhibitor (SINE) compound that works by binding and inhibiting nuclear export protein XPO1 (aka CRM1).FDA Indication: For patients with multiple myeloma (MM) who are refractory to proteasome inhibitors, immunomodulators and anti-CD38 monoclonal antibodies.Approved based on Phase IIb STORM (NCT02336815) study: an international, multicenter, single-group study to evaluate the efficacy and safety of selinexor combined with low-dose dexamethasone.The study enrolled 122 patients who had previously received three or more antimyeloma treatment regimens (including alkylating agents, glucocorticoids, bortezomib, carfilzomib, lenalidomide, pomalidomide,CD38 monoclonal antibody) and its myeloma is refractory to glucocorticoids, proteasome inhibitors, immunomodulators, anti-CD38 protein and the last therapy.Results: Selinexor combined with low-dose dexamethasone has a greater benefit-risk ratio in a subgroup of 83 patients with a total response rate (ORR) of 25.3%, reaching the median of first responseThe time was 4 weeks and the DOR was 3.8 months.Selinexor has multiple anti-tumor clinical trials, including multiple myeloma (3 clinical studies: BOSTON, STORM, STOMP), diffuse large B-cell lymphoma (SADAL study), liposarcoma (SEAL study), endometrial cancer(SIENDO study), glioblastoma (KING study), etc.Innovation: The first and only FDA-approved nuclear export inhibitor (SINE).8. Polivuz (polatuzumab vedotin-piiq) drug summary Polatuzumab vedotin-piiq is an ADC, which is a combination of humanized anti-CD79b antibody and anti-mitotic agent MMAE (monomethylastatin E), targeting CD79bSpecific expression of B cells is non-Hodgkin's lymphoma (NHL) cells.FDA approved for: combination of bendamustine and rituximab for patients with relapsed / refractory diffuse large B-cell lymphoma (R / R DLBCL) who have previously received at least 2 therapiesTreatment.Approved based on Phase Ib / II clinical study GO29365 (NCT02257567): After the Phase Ib study, 80 patients were randomly assigned to two protocol groups in the Phase II group, and one group of patients received the current first-line treatment program "bendamustine + ritualXilinumab "[BR (standard treatment group) protocol group], another group of patients received the study medication" Polatuzumab vedotin-piiq + bendamustine + rituximab "[PBR (experimental group) protocol group].Results: The complete response rate of the PBR (experimental group) protocol group reached 40% (n = 16/40, 95% CI: 25-57), and the BR (standard treatment group) protocol group was only 18% (n = 7 /40, 95% CI: 7-33).Innovation: The first chemotherapeutic immunotherapy for diffuse large B-cell lymphoma (DLBCL).9. Overview of Piqray (alpelisib) drugs Alpelisib (BYL719) is an oral PIK3CA selective inhibitor.The PI3K-Akt-mTOR signaling pathway plays an important role in cell growth, differentiation, and apoptosis. The three main nodes of the pathway, PI3K, AKT, and mTOR, have become key targets for tumor therapy.FDA approval indication: Alpelisib tablet combined with endocrine therapy fulvestrant for carrying PIK3CA gene mutation, hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative, during or after receiving endocrine therapyPatients with advanced advanced or metastatic breast cancer (including postmenopausal women and men).Related clinical trials approved: SOLAR-1 (NCT02437318) is a randomized, double-blind, placebo-controlled phase III trial involving 572 patients with HR-positive and HER2-negative advanced breast cancer.Patients were divided into two cohorts based on the PIK3CA gene mutation status of tumor tissues. Patients in both cohorts were randomly assigned to receive Alpelisib combined with fulvestrant, or placebo plus fulvestrant.Results: At a median follow-up of 20 months, in patients with PIK3CA gene mutations (n ​​= 341), the PFS of the Alpelisib combined with Fulvestrant group was 11.0 months, which was significantly longer than the Fulvestrant monotherapy group at 5.7 months.(HR for progression or death was 0.65, P <0.001).Innovation: the first PI3K inhibitor of breast cancer.10. Balversa (erdafitinib) drug overview Erdafitinib oral FGFR (fibroblast growth factor receptor) family inhibitors, FGFR signaling pathway activation in urothelial cancer, liver cancer, lung squamous cell carcinoma, bile duct cancer and many other solid tumorsIs very common.FDA Approval Indication: For adult patients with locally advanced or metastatic urothelial carcinoma (mUC) carrying specific fibroblast growth factor receptor (FGFR) gene changes, specifically: carrying susceptible FGFR3 or FGFR2 gene changes, andAdult patients with locally advanced or metastatic UC who have progressed during or after receiving at least one platinum-containing chemotherapy (including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy).Relevant clinical studies approved: The BLC2001 (NCT02365597) study is a multicenter, open-label, single-arm study involving a total of 87 patients who all underwent at least one chemotherapy or disease progression after chemotherapy and carried at least one of the followingGenetic changes: FGFR3 gene mutation (R248C, S249C, G370C, Y373C) or FGFR gene fusion (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7).. Results: Balversa treated ORR was 32.2% (95% CI: 22.4-42.0), and the responders included patients who were resistant to anti-PD-1 / PD-L1 therapy.The complete response was 2.3%, the partial response rate was 29.9%, and the median DOR was 5.4 months (95% CI: 4.3-6.9).Innovation: The first targeted therapy for metastatic bladder targeting FGFR3 or FGFR2.The above content is only authorized for exclusive use by, please do not reprint without the authorization of the copyright party.


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