The FDA on November 17, 2021, approved KEYTRUDA® (Pembrolizumab) for the adjuvant treatment of patients with Renal Cell Carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. KEYTRUDA® is a product of Merck & Co.
Author: RR
SCEMBLIX® (Asciminib)
The FDA on October 29, 2021, granted accelerated approval to SCEMBLIX® (Asciminib) for patients with Philadelphia chromosome-positive Chronic Myeloid Leukemia (Ph+ CML) in Chronic Phase (CP), previously treated with two or more Tyrosine Kinase Inhibitors (TKIs), and approved SCEMBLIX® for adult patients with Ph+ CML in CP with the T315I mutation. SCEMBLIX® is a product of Novartis AG.
TECENTRIQ® (Atezolizumab)
The FDA on October 15, 2021, approved TECENTRIQ® (Atezolizumab) for adjuvant treatment following resection and platinum-based chemotherapy in patients with Stage II to IIIA Non-Small Cell Lung Cancer (NSCLC) whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test. TECENTRIQ® is a product of Genentech, Inc.
Today, the FDA also approved the VENTANA PD-L1 (SP263) Assay (Ventana Medical Systems, Inc.) as a companion diagnostic device to select patients with NSCLC for adjuvant treatment with TECENTRIQ®.
KEYTRUDA® (Pembrolizumab)
The FDA on October 13, 2021, approved KEYTRUDA® in combination with chemotherapy, with or without Bevacizumab, for patients with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1), as determined by an FDA-approved test. KEYTRUDA® is a product of Merck & Co., Inc.
FDA also granted regular approval to KEYTRUDA® as a single agent for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. In June 2018, FDA had granted accelerated approval to this indication with the companion diagnostic, PD-L1 IHC 22C3 pharmDx (Dako North America Inc.).
VERZENIO® (Abemaciclib)
The FDA on October 12, 2021, approved VERZENIO® (Abemaciclib) with endocrine therapy (Tamoxifen or an Aromatase Inhibitor) for adjuvant treatment of adult patients with Hormone Receptor (HR)-positive, Human Epidermal growth factor Receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score ≥20%, as determined by an FDA approved test. This is the first CDK 4/6 inhibitor approved for adjuvant treatment of breast cancer. VERZENIO® is a product of Eli Lilly and Company.
FDA also approved the Ki-67 IHC MIB-1 pharmDx (Dako Omnis) assay, submitted by Agilent, Inc., as a companion diagnostic for selecting patients for this indication.
Public Human Genetic Variant Databases
The FDA on October 7, 2021, granted recognition to a partial listing of the Memorial Sloan Kettering Cancer Center’s Oncology Knowledge Base (OncoKB) as the first tumor mutation database to be included in the Public Human Genetic Variant Databases.
TECARTUS® (Brexucabtagene autoleucel)
The FDA on October 1, 2021, approved TECARTUS® (Brexucabtagene autoleucel) for adult patients with Relapsed or Refractory B-cell precursor Acute Lymphoblastic Leukemia (ALL). TECARTUS® is a product of Kite Pharma, Inc.
JAKAFI® (Ruxolitinib)
The FDA on September 22, 2021 approved JAKAFI® (Ruxolitinib) for chronic Graft-Versus-Host Disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. JAKAFI® is a product of Incyte Corp.
TIVDAK® (Tisotumab vedotin-tftv)
The FDA on September 20, 2021 granted accelerated approval to TIVDAK®, a tissue factor-directed antibody and microtubule inhibitor conjugate, for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
TIVDAK® is a product of Seagen Inc.
FDA Approves PSMA Targeted Therapy for Metastatic Castrate Resistant Prostate Cancer
SUMMARY: The FDA on March 23, 2022, approved PLUVICTO® (Lutetium Lu 177 vipivotide tetraxetan) for the treatment of adult patients with Prostate-Specific Membrane Antigen (PSMA)-positive metastatic Castration-Resistant Prostate Cancer (mCRPC), who had been treated with Androgen Receptor (AR) pathway inhibition and Taxane-based chemotherapy. The FDA also approved LOCAMETZ® (Gallium Ga 68 gozetotide), a radioactive diagnostic agent for Positron Emission Tomography (PET) of PSMA-positive lesions, including selection of patients with metastatic prostate cancer for whom PLUVICTO® PSMA-directed therapy is indicated. LOCAMETZ® is the first radioactive diagnostic agent approved for patient selection in the use of a radioligand therapeutic agent.
The development and progression of prostate cancer is driven by androgens. Androgen Deprivation Therapy (ADT) or testosterone suppression has therefore been the cornerstone of treatment of advanced prostate cancer, and is the first treatment intervention. Approximately 10-20% of patients with advanced Prostate cancer will progress to Castration Resistant Prostate Cancer (CRPC) within five years during ADT, and over 80% of these patients will have metastatic disease at the time of CRPC diagnosis. Among those patients without metastases at CRPC diagnosis, 33% are likely to develop metastases within two years. Progression to Castration Resistant Prostate Cancer (CRPC) often manifests itself with a rising PSA (Prostate Specific Antigen) and the estimated mean survival of patients with CRPC is 9-36 months, and there is therefore an unmet need for new effective therapies.
Prostate-Specific Membrane Antigen (PSMA) is a Type II cell membrane glycoprotein that is selectively expressed in prostate cells, with high levels of expression in prostatic adenocarcinoma. PSMA is a therefore an excellent target for molecular imaging and therapeutics, due to its high specificity for prostate cancer.
PLUVICTO® is a radiopharmaceutical that targets PSMA. It is comprised of Lutetium-177, a cytotoxic radionuclide , linked to the ligand PSMA-617, a small molecule designed to bind with high affinity to PSMA. Radioligand therapy with PLUVICTO® targets PSMA and releases its payload of lethal beta radiation into the prostate cancer cell. The antitumor activity and safety PLUVICTO® have been established previously in a Phase II study (Lancet Oncol. 2018;19:825-833).
VISION is an international, randomized, open-label Phase III study in which the benefit of PLUVICTO® was evaluated in men with PSMA-positive mCRPC, previously treated with second generation Androgen Receptor signaling pathway inhibitor (XTANDI® -Enzalutamide or ZYTIGA®-Abiraterone acetate), and 1 or 2 taxane chemotherapy regimens. In this trial, 831 patients were randomized 2:1 to receive PLUVICTO® 7.4 GBq (200 mCi) every 6 weeks for up to a total of 6 cycles plus Standard of Care as determined by the treating physician (N=551), or Standard of Care only (N=280). Both treatment groups were well balanced and this trial excluded patients treated with XOFIGO® (Radium-223). All enrolled patients received a GnRH analog or had prior bilateral orchiectomy and had a castrate level or serum/plasma testosterone of lower than 50ng/dL. PET imaging with LOCAMETZ® was used to determine PSMA positivity by central review. PSMA-positive mCRPC was defined as having at least one tumor lesion with LOCAMETZ® uptake greater than normal liver. Patients were excluded from enrollment if any lesions exceeding certain size criteria in the short axis had uptake less than or equal to uptake in normal liver. The Primary endpoints were radiographic Progression Free Survival (rPFS) by Independent Central Review (ICR) and Overall Survival (OS). Secondary endpoints included Objective Response Rate (ORR), Disease Control Rate (DCR), and time to first Symptomatic Skeletal Event (SSE). The median study follow up was 20.9 months.
Treatment with the combination of PLUVICTO® plus Standard of Care resulted in a statistically significant improvement in the Primary endpoints of Overall Survival and radiographic Progression Free Survival. PLUVICTO® plus Standard of Care significantly improved rPFS by 60%, compared to Standard of Care alone (median rPFS 8.7 versus 3.4 months, HR=0.40; P<0.001). The median OS was also significantly improved by 38% in the study group (median OS 15.3 versus 11.3 months, HR=0.62; P<0.001). All key secondary endpoints including Objective Response Rate, Disease Control Rate, and time to first Symptomatic Skeletal Event were statistically significant, and in favor of PLUVICTO® plus Standard of Care. The most common adverse reactions in patients receiving PLUVICTO® were fatigue, dry mouth, nausea, decreased appetite, constipation, anemia, lymphopenia, thrombocytopenia, hypocalcemia and hyponatremia.
It was concluded that radioligand therapy with PLUVICTO® significantly improved radiographic Progression Free Survival and Overall Survival when added to Standard of Care, compared with Standard of Care alone, in men with PSMA-positive metastatic Castration Resistant Prostate Cancer.
Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. Sartor O, de Bono J, Chi KN, et al. N Engl J Med 2021; 385:1091-1103.