This section provides a brief overview of new cancer drugs or new indications approved by the FDA between September 1, 2020, and December 1, 2020.
- FDA Approves First Prostate-Specific Membrane Antigen–Targeted PET Imaging Drug for Prostate Cancer
- Danyelza First Drug FDA Approved for High-Risk Neuroblastoma in the Bone and Bone Marrow
- Gavreto, a New RET Inhibitor, FDA Approved for Metastatic NSCLC with RET fusions
- Oral Onureg FDA Approved for Adults with AML in Remission
- Gavreto Now Approved for Thyroid Cancer with RET Fusions
- Keytruda plus Chemotherapy Approved for Unresectable or Metastatic Triple‑Negative Breast Cancer
- Keytruda Approved for Relapsed or Refractory Classical Hodgkin Lymphoma
- Opdivo plus Yervoy First Immunotherapy Approved for Unresectable Malignant Pleural Mesothelioma
FDA Approves First Prostate-Specific Membrane Antigen–Targeted PET Imaging Drug for Prostate Cancer
On December 1, 2020, the FDA approved Gallium 68 PSMA-11 (Ga 68 PSMA-11; University of California), the first drug for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA)-positive lesions in men with prostate cancer. Ga 68 PSMA-11 is indicated for men with suspected metastatic prostate cancer that may be curable by surgery or by radiation, and for suspected recurrent prostate cancer based on elevated serum prostate-specific antigen (PSA) levels.
Ga 68 PSMA-11 is a radioactive drug that is administered via intravenous injection. Ga 68 PSMA-11 binds to PSMA, an important target for prostate cancer imaging.
The approval of Ga 68 PSMA-11 was based on the results of 2 prospective clinical trials in 960 men with prostate cancer who received 1 Ga 68 PSMA-11 with PET and computed tomography or with PET and magnetic resonance imaging. In the first study, 325 patients were candidates for surgery or had an increased risk for metastasis. Among the patients who had surgery, positive readings in the pelvic lymph nodes on Ga 68 PSMA-11 PET had a clinically significant rate of metastatic cancer confirmed by surgical pathology.
The second study included 635 patients with biochemical evidence of recurrent prostate cancer. In all, 74% of the patients had ≥1 positive lesions, as detected by Ga 68 PSMA-11 PET in at least 1 body region. Of those with positive Ga 68 PSMA-11 PET readings and correlative tissue pathology from biopsies, the results from baseline or follow-up imaging by conventional methods, and the serial PSA levels, 91% had confirmed local recurrence or metastasis of prostate cancer.
No serious adverse events were seen with Ga 68 PSMA-11. The most common adverse reactions were nausea, diarrhea, and dizziness. This drug is associated with a risk for misdiagnosis, because Ga 68 PSMA-11 binding may occur in other types of cancer, as well as certain nonmalignant processes.
Danyelza First Drug FDA Approved for High-Risk Neuroblastoma in the Bone and Bone Marrow
On November 25, 2020, the FDA granted accelerated approval to naxitamab-gqgk (Danyelza; Y-mAbs Therapeutics), a GD2-binding monoclonal antibody, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow in pediatric patients aged ≥1 year and adults > achieved a partial response, minor response, or stable disease after receiving previous therapy. The FDA granted naxitamab priority review and breakthrough therapy, orphan drug, and rare pediatric disease designations.
“We believe that Danyelza in combination with GM-CSF is a much-needed treatment for patients with relapsed/refractory high-risk neuroblastoma in the bone or bone marrow who have historically not had approved treatments available,” said Claus Moller, Chief Executive Officer, Y-mAbs Therapeutics.
The approval of naxitamab was based on the results of 2 single-arm, open-label clinical trials in patients with relapsed or refractory neuroblastoma in the bone or bone marrow. The patients received naxitamab 3 mg/kg via intravenous infusion on days 1, 3, and 5 of each 4-week cycle in combination with GM-CSF subcutaneously at 250 µg/m2 daily on days –4 to 0 and at 500 µg/m2/day on days 1 to 5. The cycles were repeated every 4 to 8 weeks. At the investigator’s discretion, the patients received preplanned radiation to the main disease site in Study 201 and radiation therapy to nontargeted bony lesions or soft-tissue disease in Study 12-230.
The primary end points were overall response rate (ORR) per the revised International Neuroblastoma Response Criteria, and the duration of response (DOR). The ORR in Study 201 (N = 22) was 45% (95% confidence interval (CI), 24%-68%), and 30% of responders had a DOR of ≥6 months. In Study 12-230 (N = 38), the ORR was 34% (95% CI, 20%-51%), with a DOR of ≥6 months in 23% of responders. The responses were in the bone, the bone marrow, or in both.
The most common (≥25%) adverse reactions with naxitamab were infusion-related reactions, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection-site reaction, edema, anxiety, localized edema, and irritability.
Grade 3 or 4 adverse events (≥5%) were decreased levels of lymphocyte count, neutrophil count, hemoglobin, platelet count, potassium, glucose, calcium, albumin, sodium, and phosphate; and increased alanine aminotransferase.
Gavreto, a New RET Inhibitor, FDA Approved for Metastatic NSCLC with RET fusions
On September 4, 2020, the FDA accelerated the approval of pralsetinib (Gavreto; Blueprint Medicines), an oral RET inhibitor, for the treatment of adults with metastatic non–small-cell lung cancer (NSCLC) and RET-activating fusions, as detected by an FDA-approved test.
The FDA granted pralsetinib a breakthrough therapy designation for the treatment of NSCLC and RET fusion that has progressed after platinum-based chemotherapy, as well as for patients with medullary thyroid cancer and RET mutation that requires systemic treatment and for which there are no acceptable alternative treatments.
RET-activating fusions and mutations are key drivers in many cancer types, including NSCLC and medullary thyroid cancer. Currently, there are limited targeted treatments for patients with these types of genetic alterations. Approximately 1% to 2% of people with NSCLC have RET fusions. Biomarker testing for these fusions is the most effective way to identify people who are eligible for treatment with pralsetinib.
“The FDA approval of Gavreto for RET fusion-positive non–small-cell lung cancer is an important step towards our goal of providing an effective treatment option for every person diagnosed with lung cancer, no matter how rare or hard-to-treat their type of disease,” said Levi Garraway, MD, PhD, Chief Medical Officer and Head of Global Product Development at Genentech. “We remain committed to finding personalized treatment options for people with cancer based on specific genomic or molecular alterations, and we look forward to partnering with Blueprint Medicines to further explore the potential of Gavreto across multiple RET-altered tumor types.”
The FDA approved pralsetinib for this indication based on the results of the phase 1/2 ARROW clinical trial, a first-in-human study that is evaluating the safety and efficacy of pralsetinib in patients with NSCLC or thyroid cancer that is associated with RET fusions or mutations. Patients receive 400 mg of pralsetinib orally once daily.
Among the 87 patients with NSCLC who have previously received platinum-based chemotherapy, the overall response rate (ORR) with pralsetinib was 57% (95% confidence interval [CI], 46%-68%), including a 5.7% complete response rate. The median duration of response has not been reached (95% CI, 15.2 months-not reached).
In the 27 people with treatment-naïve NSCLC, the ORR was 70% (95% CI, 50%-86%), including 11% complete responses.
The most common (≥25%) adverse reactions with pralsetinib were fatigue, constipation, musculoskeletal pain, and hypertension.
Oral Onureg FDA Approved for Adults with AML in Remission
On September 1, 2020, the FDA approved azacitidine (Onureg; Celgene), an oral nucleoside metabolic inhibitor, for continued treatment of adults with acute myeloid leukemia (AML) who had first complete remission (CR) or CR with incomplete blood count recovery after intensive induction chemotherapy and who are not candidates for intensive curative therapy. The FDA granted azacitidine an orphan drug designation and used its priority review for this indication.
The FDA approved azacitidine based on the results of the QUAZAR study, a multicenter, randomized, double-blind, placebo-controlled clinical trial of 472 patients with AML who achieved CR or CR with incomplete blood count recovery. The patients were randomized in a 1:1 ratio to azacitidine 300 mg (N = 238) or to placebo (N = 234) on days 1 to 14 of each 28-day cycle. The primary end point was overall survival (OS).
The median OS was 24.7 months 18.7-30.5) in the azacitidine arm versus 14.8 months in the placebo arm (hazard ratio, 0.69; 95% confidence interval, 0.55-0.86; P = .0009). A subgroup analysis showed consistent OS benefits with azacitidine in patients with CR or with CR and incomplete blood count recovery.
The most common (≥10%) adverse reactions with azacitidine were nausea, vomiting, diarrhea, fatigue/asthenia, constipation, pneumonia, abdominal pain, arthralgia, decreased appetite, febrile neutropenia, dizziness, and pain in an extremity.
The recommended dose of azacitidine is 300 mg orally once daily, on days 1 to 14 of each 28-day cycle.
Gavreto Now Approved for Thyroid Cancer with RET Fusions
On December 1, 2020, the FDA accelerated the approval of a new indication for pralsetinib (Gavreto; Blueprint Medicines), a RET kinase inhibitor, for the treatment of patients aged ≥12 years with advanced or metastatic medullary thyroid cancer and RET mutation who require systemic therapy or for patients with thyroid cancer and RET fusion who require systemic therapy and whose tumor is refractory to radioactive iodine, if radioactive iodine is appropriate.
The FDA granted pralsetinib priority review and orphan drug and breakthrough therapy designations for thyroid cancer with RET fusions. In September 2020, the FDA approved pralsetinib for metastatic non–small-cell lung cancer and RET fusions in adults.
The new indication was based on the overall response rate (ORR) and duration of response reported in the ARROW study, a multicenter, open-label, multicohort clinical trial of 55 patients with advanced or metastatic medullary thyroid cancer and RET alterations.
In the 55 patients with RET mutations who previously receive cabozantinib (Cabometyx) or vandetanib was 60%, with 79% of the responses lasting for ≥6 months. Among 29 patients with RET mutations who did not receive previous treatment with cabozantinib or vandetanib, and in 9 patients with thyroid cancer and RET fusion who were refractory to radioactive iodine the ORRs were 66% and 89%, respectively, and the responses lasted ≥6 months in 84% and 100% of the patients, respectively.
The most common (≥25%) adverse reactions with pralsetinib were constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea. The most common (≥2%) grade 3 or 4 were decreased levels of lymphocytes, neutrophils, platelets, hemoglobin, decreased phosphate, calcium (corrected), and sodium, and increased levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase.
Keytruda plus Chemotherapy Approved for Unresectable or Metastatic Triple‑Negative Breast Cancer
On November 13, 2020, the FDA accelerated the approval of pembrolizumab (Keytruda; Merck), a PD-1 inhibitor, plus chemotherapy, for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) in patients with PD-L1 (combined positive score [CPS] ≥10), as determined by an FDA-approved test.
“Approximately 15% to 20% of patients with breast cancer are diagnosed with triple-negative breast cancer, which is a difficult-to-treat and aggressive cancer,” said Hope S. Rugo, MD, FASCO, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco.
The FDA accelerated this approval based on the KEYNOTE-355 study, a multicenter, randomized, double-blind, phase 3 study of 847 patients with locally recurrent unresectable or metastatic TNBC. The patients had not received chemotherapy in the metastatic setting and were randomized to pembrolizumab plus chemotherapy versus chemotherapy and placebo.
The main efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumours criteria version 1.1, which was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ in the subgroup of patients with tumors expressing PD-L1 (CPS ≥10). Additional efficacy outcome measures included overall survival, objective response rate (ORR), and duration of response (DOR) as assessed by blinded independent central review.
Pembrolizumab in combination with chemotherapy significantly reduced the risk for disease progression and death by 35% in the patients whose tumors expressed PD-L1 (CPS ≥10) versus with the same chemotherapy regimens alone (hazard ratio, 0.65; 95% confidence interval [CI], 0.49-0.86; P = .0012); the median PFS was 9.7 months (95% CI, 7.6-11.3) versus 5.6 months (95% CI, 5.3-7.5), respectively. Adverse events were observed in 136 (62%) of the 220 patients who received pembrolizumab plus chemotherapy versus 79 (77%) of the 103 patients who received chemotherapy alone. The ORRs were 53% and 40%, respectively, and the DOR was 19.3 months and 7.3 months, respectively, in the pembrolizumab plus chemotherapy group versus the chemotherapy-alone group.
Fatal adverse reactions occurred in 2.5% of patients who received pembrolizumab plus chemotherapy. The most common (≥20%) adverse events in the pembrolizumab arm were fatigue, nausea, alopecia, diarrhea, constipation, vomiting, rash, cough, decreased appetite, and headache.
Keytruda Approved for Relapsed or Refractory Classical Hodgkin Lymphoma
On October 14, 2020, the FDA expanded the approval of pembrolizumab (Keytruda; Merck), a PD-1 inhibitor, for the treatment of relapsed or refractory classical Hodgkin lymphoma in adults and for refractory classical Hodgkin lymphoma or classical Hodgkin lymphoma in pediatric patients that has relapsed after receiving ≥2 lines of therapy. The FDA granted pembrolizumab orphan drug and breakthrough therapy designations for this indication.
This approval was based on the results of the KEYNOTE-204 study, a phase 3, randomized, open-label clinical trial of 304 adults with relapsed or refractory classical Hodgkin lymphoma. The patients were randomized in a 1:1 ratio to pembrolizumab 200 mg every 3 weeks or to brentuximab vedotin (Adcetris) 1.8 mg/kg every 3 weeks for up to 2 years.
The efficacy of pembrolizumab in adults and pediatric patients with relapsed or refractory classical Hodgkin lymphoma was based on progression-free survival (PFS). The PFS was significantly longer in the pembrolizumab arm versus the brentuximab vedotin arm. The median PFS was 13.2 months in the pembrolizumab arm and 8.3 months in the brentuximab vedotin arm (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88; P = .0027).
Serious adverse reactions occurred in 30% of the patients who received pembrolizumab.
Opdivo plus Yervoy First Immunotherapy Approved for Unresectable Malignant Pleural Mesothelioma
On October 2, 2020, the FDA approved the combination of nivolumab (Opdivo; Bristol Myers Squibb), a PD-1 inhibitor, and ipilimumab (Yervoy; Bristol Myers Squibb), a CTLA-4 inhibitor, for first-line treatment of adults with unresectable malignant pleural mesothelioma.
“Malignant pleural mesothelioma is a rare cancer with limited treatment options. When it is diagnosed in advanced stages, the 5-year survival rate is approximately 10%,” said study investigator Anne S. Tsao, MD, Professor and Section Chief, Thoracic Medical Oncology, and Director of the Mesothelioma Program at M.D. Anderson Cancer Center, Houston, in a press release. “The survival results from the CheckMate-743 trial show that the combination of nivolumab and ipilimumab could become a new front-line standard of care option. This is exciting news, instilling hope for patients with this devastating disease and for the healthcare providers who care for them.”
This new indication for the immunotherapy combination was based on the results of a prespecified interim analysis of the CheckMate-743 study, a phase 3, randomized, open-label clinical trial in treatment-naïve patients with unresectable malignant pleural mesothelioma. Patients were randomized to the immunotherapy combination (N = 303) or to a chemotherapy combination with cisplatin or carboplatin, plus pemetrexed (Alimta; N = 302).
At a 22-month follow up, the median overall survival was 18.1 months with the immunotherapy combination versus 14.1 months with chemotherapy plus pemetrexed (hazard ratio, 0.74; 95% confidence interval, 0.61-0.89; P = .002). At 2 years, 41% of the patients who received immunotherapy were alive versus 27% of those who received chemotherapy.
The most common (≥20%) adverse reactions with nivolumab plus ipilimumab were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.