This section provides a brief overview of new cancer drugs and new indications approved by the FDA between October 21, 2022, and December 1, 2022.
- Rezlidhia New IDH1 Inhibitor FDA Approved for Relapsed or Refractory AML with IDH1 Mutation
- Elahere, First FRα-Directed Antibody, FDA Approved for FRα-Positive, Platinum-Resistant Ovarian Cancer
- Tecvayli, First Bispecific BCMA-Directed CD3 T-Cell Engager, FDA Approved for Relapsed or Refractory Multiple Myeloma
- Imjudo, a New CTLA-4 Inhibitor, FDA Approved in Combination with Imfinzi for Unresectable Hepatocellular Carcinoma
- Imjudo FDA Approved with Imfinzi and Chemotherapy for Metastatic NSCLC
- Rylaze Received FDA Approval of a New Dosing Regimen
- Adcetris plus Chemotherapy Now FDA Approved for Pediatric Patients with Hodgkin Lymphoma
- Libtayo plus Platinum-Based Chemotherapy Now FDA Approved for NSCLC without Genomic Aberrations
NEW DRUGS
Rezlidhia New IDH1 Inhibitor FDA Approved for Relapsed or Refractory AML with IDH1 Mutation
On December 1, 2022, the FDA approved olutasidenib (Rezlidhia; Forma Therapeutics) capsules, an oral IDH1 inhibitor, for adults with relapsed or refractory acute myeloid leukemia (AML) and a susceptible IDH1 mutation, as detected by an FDA-approved test.
On the same day, the FDA approved the Abbott RealTime IDH1 Assay to identify candidates for treatment with olutasidenib.
The FDA approval of olutasidenib was based on Study 2102-HEM-101, an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML and an IDH1 mutation, which was confirmed using the Abbott RealTime IDH1 Assay.
Patients received olutasidenib 50 mg twice daily orally until disease progression, unacceptable adverse events, or hematopoietic stem-cell transplantation. The median treatment duration was 4.7 months (range, 0.1-26 months), and 16 (11%) patients underwent a transplant after receiving olutasidenib.
Key efficacy measures were complete remission (CR) plus CR with partial hematologic recovery (CRh), the duration of CR+CRh, and conversion from transfusion dependence to independence.
The CR+CRh rate was 35% (95% confidence interval [CI], 27%-43%), including 32% CRs and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5-not reached).
Of the 86 patients who were receiving red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and/or platelet transfusions during any 56-day postbaseline. Of the 61 patients who were independent of RBC and/or platelet transfusions at baseline, 39 (64%) remained transfusion independent during any 56-day postbaseline.
The most common (≥20%) adverse events were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.
The prescribing information of olutasidenib contains a boxed warning about the risk of differentiation syndrome.
The recommended dose is 150 mg orally, taken twice daily ≥1 hour before or ≥2 hours after a meal, for at least 6 months to allow for response, or until disease progression or unacceptable side effects.
Elahere, First FRα-Directed Antibody, FDA Approved for FRα-Positive, Platinum-Resistant Ovarian Cancer
On November 14, 2022, the FDA accelerated the approval of mirvetuximab soravtansine-gynx (Elahere; ImmunoGen), an intravenous folate receptor alpha (FRα)-directed antibody and microtubule inhibitor conjugate, for the treatment of adults with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer after 1 to 3 previous systemic treatments, regardless of previous use of bevacizumab (Avastin). Patients should be identified for treatment with mirvetuximab soravtansine by an FDA-approved test.
Mirvetuximab soravtansine is the first FRα-directed antibody–drug conjugate approved by the FDA.
On the same day, the FDA approved the VENTANA FOLR1 RxDx Assay, a companion diagnostic test to mirvetuximab soravtansine.
The efficacy of mirvetuximab soravtansine was evaluated in the SORAYA study, a single-arm clinical trial of 106 patients with FRα-positive, platinum-resistant epithelial ovarian cancer. The drug’s safety was evaluated in a pooled analysis of 3 studies that included 464 patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Patients were allowed to have up to 3 previous lines of systemic therapy, regardless of bevacizumab use. Patients with FRα-positive disease were identified by the VENTANA FOLR1 RxDx Assay. Patients were excluded from the study if they had corneal disorders, ocular conditions requiring ongoing treatment, grade >1 peripheral neuropathy, or noninfectious interstitial lung disease.
All patients received mirvetuximab soravtansine 6 mg/kg (based on adjusted ideal body weight) as an intravenous (IV) infusion every 3 weeks, until disease progression or unacceptable adverse events. Response to therapy was evaluated every 6 weeks for the first 36 weeks, and every 12 weeks thereafter.
The main efficacy measures were overall response rate (ORR) and duration of response (DOR). Among the 104 patients with platinum-resistant disease who received ≥1 doses of mirvetuximab soravtansine, the ORR was 31.7% (95% confidence interval [CI], 22.9-41.6), including 5 complete responses, and the median DOR was 6.9 months (95% CI, 5.6-9.7).
The most common (≥20%) adverse events with mirvetuximab soravtansine were vision impairment, dry eye, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, decreased magnesium, decreased leukocytes, decreased neutrophils, and decreased hemoglobin.
The prescribing information for mirvetuximab soravtansine includes a boxed warning for ocular adverse events, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis.
The recommended dose of mirvetuximab soravtansine is 6 mg/kg once every 3 weeks as an IV infusion until disease progression or unacceptable adverse events.
Tecvayli, First Bispecific BCMA-Directed CD3 T-Cell Engager, FDA Approved for Relapsed or Refractory Multiple Myeloma
On October 25, 2022, the FDA accelerated the approval of teclistamab-cqyv (Tecvayli; Janssen Biotech), the first bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for the treatment of adults with relapsed or refractory multiple myeloma who received ≥4 previous lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody. The FDA granted teclistamab breakthrough therapy and orphan drug designations.
The FDA approved teclistamab based on the results of the MajesTEC-1 clinical trial, a single-arm, multicohort, open-label, multicenter study. The efficacy was evaluated in 110 patients who had received ≥3 previous therapies, including a PI, an IMiD, and an anti-CD38 monoclonal antibody, and had not received previous BCMA-targeted therapy.
The overall response rate, the study’s main efficacy measure, with teclistamab was 61.8% (95% confidence interval [CI], 52.1-70.9). With a median follow-up of 7.4 months, the estimated duration of response was 90.6% (95% CI, 80.3%-95.7%) at 6 months and 66.5% (95% CI, 38.8%-83.9%) at 9 months.
The most common (≥20%) adverse events in the 165 patients in the safety population were pyrexia, cytokine release syndrome (CRS), musculoskeletal pain, injection-site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common (≥20%) grade 3 or 4 laboratory events were decreased levels of lymphocytes, neutrophils, white blood cells, hemoglobin, and platelets.
The prescribing information for teclistamab includes a boxed warning regarding CRS and neurologic adverse events, including immune effector cell–associated neurotoxicity syndrome (ICANS). In the study, 72% of the patients had CRS, including 0.6% grade 3; 57% had neurologic adverse events, including 2.4% grade 3 or 4; and 6% had ICANS. Therefore, teclistamab was approved with a REMS (Risk Evaluation and Mitigation Strategy) program.
The recommended dose of teclistamab is 0.06 mg/kg by subcutaneous injection on day 1, 0.3 mg/kg on day 4, and 1.5 mg/kg on day 7, followed by 1.5 mg/kg once weekly, until disease progression or unacceptable adverse events.
Imjudo, a New CTLA-4 Inhibitor, FDA Approved in Combination with Imfinzi for Unresectable Hepatocellular Carcinoma
On October 21, 2022, the FDA approved tremelimumab (Imjudo; AstraZeneca), a CTLA-4 monoclonal antibody, in combination with durvalumab (Imfinzi; AstraZeneca), a PD-L1 inhibitor, for the treatment of adults with unresectable hepatocellular carcinoma (HCC). The FDA granted tremelimumab an orphan drug designation for this indication.
The efficacy of this new dual immunotherapy combination was evaluated in the HIMALAYA study, a randomized, open-label, multicenter clinical trial of patients with unresectable HCC who had not received systemic treatment for HCC. Patients were randomized to 1 of 4 arms: (1) tremelimumab 300 mg as a single intravenous (IV) infusion in combination with durvalumab 1500 mg IV, followed by durvalumab 1500 mg IV every 4 weeks; (2) durvalumab 1500 mg IV every 4 weeks; (3) sorafenib (Nexavar) 400 mg, orally, twice daily; or (4) tremelimumab 75 mg every 4 weeks plus durvalumab every 4 weeks. Treatment continued until disease progression or unacceptable adverse events.
The FDA approval of this combination was based on a comparison of 782 patients who were randomized to the tremelimumab plus durvalumab arm versus those in the sorafenib arm.
The main efficacy outcome was overall survival (OS). Tremelimumab plus durvalumab in arm 1 showed significant and meaningful improvements in OS compared with sorafenib (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.66-0.92; 2-sided P = .0035). The median OS was 16.4 months (95% CI, 14.2-19.6) versus 13.8 months (95% CI, 12.3-16.1), respectively.
Additional efficacy outcomes were progression-free survival (PFS) and overall response rate (ORR). The median PFS was 3.8 months (95% CI, 3.7-5.3) with the combination versus 4.1 months (95% CI, 3.7-5.5) with sorafenib (HR, 0.90). The ORR was 20.1% (95% CI, 16.3-24.4) with the combination versus 5.1% (95% CI, 3.2-7.8) with sorafenib.
The most common (≥20%) adverse events with the immunotherapy combination were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.
The recommended tremelimumab dose for patients weighing ≥30 kg is 300 mg IV as a single dose, in combination with durvalumab 1500 mg at cycle 1, day 1, followed by durvalumab 1500 mg IV every 4 weeks. For those weighing <30 kg, the recommended tremelimumab dose is 4 mg/kg IV as a single dose, in combination with durvalumab 20 mg/kg IV, followed by durvalumab 20 mg/kg IV every 4 weeks.
Imjudo FDA Approved with Imfinzi and Chemotherapy for Metastatic NSCLC
Two weeks after the initial approval of tremelimumab (Imjudo; AstraZeneca), a CTLA-4 monoclonal antibody, on November 10, 2022, the FDA approved this new immunotherapy, in combination with the PD-L1 inhibitor durvalumab (Imfinzi; AstraZeneca) and platinum- based chemotherapy, for the treatment of adults with metastatic non–small-cell lung cancer (NSCLC) and no EGFR or ALK genomic alterations.
The efficacy of this immunotherapy combination plus chemotherapy was evaluated in the phase 3 POSEIDON clinical trial, a randomized, multicenter, open-label study of patients with metastatic NSCLC who had not received systemic treatment. Patients were randomized to 1 of 3 treatment arms: (1) tremelimumab, durvalumab, and platinum-based chemotherapy for 4 cycles, followed by durvalumab and maintenance chemotherapy every 4 weeks, and a fifth dose of tremelimumab at week 16; (2) durvalumab plus platinum-based chemotherapy for 4 cycles, followed by durvalumab and maintenance chemotherapy; or (3) platinum-based chemotherapy for 6 cycles, followed by maintenance chemotherapy. Treatment was continued until disease progression or unacceptable adverse events.
The FDA approval was based on the results of the 675 patients in arms 1 and 3. The main efficacy measures were progression-free survival (PFS) and overall survival (OS). Tremelimumab plus durvalumab and chemotherapy showed a significant and clinically meaningful improvement in OS versus chemotherapy alone (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65-0.92; 2-sided P = .00304).
The median OS was 14 months (95% CI, 11.7-16.1) with the triplet combination versus 11.7 months (95% CI, 10.5-13.1) with chemotherapy alone. The median PFS was 6.2 months (95% CI, 5.0-6.5) and 4.8 months (95% CI, 4.6-5.8), respectively (HR, 0.72; 2-sided P = .00031). The overall response rate was 39% versus 4%, respectively, and the median duration of response was 9.5 months versus 5.1 months, respectively.
The most common (≥20%) adverse events with the triplet were nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhea. Grade 3 or 4 laboratory abnormalities (≥10%) were neutropenia, anemia, leukopenia, lymphocytopenia, increased lipase, hyponatremia, and thrombocytopenia.
The recommended dose of tremelimumab for patients weighing ≥30 kg is 75 mg intravenous (IV) every 3 weeks with durvalumab 1500 mg IV and platinum-based chemotherapy for 4 cycles, then durvalumab 1500 mg and maintenance chemotherapy every 4 weeks. A fifth dose of tremelimumab 75 mg should be given at week 16.
For patients weighing ≤30 kg, the recommended tremelimumab dose is 1 mg/kg and the durvalumab dose is 20 mg/kg, using the same schedule as above.
NEW INDICATIONS
Rylaze Received FDA Approval of a New Dosing Regimen
On November 18, 2022, the FDA approved a new dosing regimen for asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze; Jazz Pharmaceuticals). With this new regimen, asparaginase erwinia chrysanthemi (recombinant) is administered as 25 mg/m2 intramuscularly on Monday and Wednesday mornings, and 50 mg/m2 intramuscularly on Friday afternoon. The drug is also approved at a dose of 25 mg/m2 intramuscularly every 48 hours.
Asparaginase erwinia chrysanthemi (recombinant) was previously approved as a component of a multi-agent chemotherapy regimen for patients aged ≥1 month with acute lymphoblastic leukemia or lymphoblastic lymphoma who have hypersensitivity to Escherichia coli–derived asparaginase.
This new dosing regimen was approved based on results in 225 patients in the open-label multicenter Study JZP458-201. In the study, the drug was used at various dosages and routes of administration, and the results were used to develop a model to predict the serum asparaginase activity at various time points.
All patients who received the recommended dosages of asparaginase erwinia chrysanthemi (recombinant) as a component of a multi-agent chemotherapy regimen had neutropenia, anemia, or thrombocytopenia. The most common (>20%) nonhematologic adverse events were abnormal liver test, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage, stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia.
Adcetris plus Chemotherapy Now FDA Approved for Pediatric Patients with Hodgkin Lymphoma
On November 10, 2022, the FDA approved brentuximab vedotin (Adcetris; Seagen) in combination with a chemotherapy regimen of doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (AVEPC) for treatment-naïve pediatric patients aged ≥2 years with high-risk classical Hodgkin lymphoma. This is the first indication for brentuximab vedotin for pediatric patients. Brentuximab vedotin has an orphan drug designation for Hodgkin lymphoma.
This drug was previously approved for classical Hodgkin lymphoma in adults, and for adults with various types of anaplastic large-cell lymphoma.
The FDA approval of this new indication was based on results of a randomized, open-label, actively controlled clinical trial. High-risk Hodgkin lymphoma was classified as Ann Arbor stage IIB with bulk disease, stage IIIB, stage IVA, or stage IVB. The total 600 patients were randomized in a 1:1 ratio to brentuximab vedotin plus AVEPC or to a chemotherapy regimen with doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). Patients in each arm received up to 5 cycles of the respective drug regimen.
Patients in the brentuximab vedotin plus AVEPC arm received brentuximab vedotin 1.8 mg/kg over 30 minutes (day 1), doxorubicin 25 mg/m2 (days 1 and 2), vincristine 1.4 mg/m2 (day 8), etoposide 125 mg/m2 (days 1-3), prednisone 20 mg/m2 twice daily (days 1-7), and cyclophosphamide 600 mg/m2 (days 1 and 2). In the ABVE-PC arm, patients received doxorubicin 25 mg/m2 (days 1 and 2), bleomycin 5 units/m2 (day 1) and 10 units/m2 (day 8), vincristine 1.4 mg/m2 (days 1 and 8), etoposide 125 mg/m2 (days 1-3), prednisone 20 mg/m2 twice daily (days 1-7), and cyclophosphamide 600 mg/m2 (days 1 and 2).
The main efficacy measure was event-free survival (EFS), defined as the time from randomization to the earliest of disease progression or relapse, second malignancy, or death from any cause. The median EFS was not reached in either arm.
A total of 23 (8%) adverse events occurred in the brentuximab vedotin plus AVEPC arm versus 52 (17%) events in the ABVE-PC arm. The most common (≥5%) grade 3 or 4 adverse events with brentuximab vedotin plus AVEPC in pediatric patients were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection.
Libtayo plus Platinum-Based Chemotherapy Now FDA Approved for NSCLC without Genomic Aberrations
On November 8, 2022, the FDA approved a new indication for cemiplimab-rwlc (Libtayo; Regeneron), a PD-1 inhibitor, in combination with platinum-based chemotherapy, for the treatment of adults with advanced non–small-cell lung cancer (NSCLC) and no EGFR, ALK, or ROS1 aberrations.
Libtayo was previously approved for first-line treatment of advanced or metastatic NSCLC with PD-1 expression of ≥50% but with no EGFR, ALK, or ROS1 aberrations, in addition to the treatment of cutaneous squamous-cell carcinoma and basal-cell carcinoma.
The FDA approved this new indication based on results of Study 1611, a randomized, multicenter, multinational, double-blind, active-controlled clinical trial of 466 patients with advanced NSCLC who had not received systemic treatment.
The patients were randomized in a 2:1 ratio to cemiplimab plus platinum-based chemotherapy every 3 weeks for 4 cycles, followed by cemiplimab and maintenance chemotherapy, or to placebo plus platinum-based chemotherapy every 3 weeks for 4 cycles, followed by placebo and maintenance chemotherapy.
The main efficacy measure was overall survival (OS). Additional measures were progression-free survival (PFS) and overall response rate (ORR).
Cemiplimab plus chemotherapy demonstrated significant and clinically meaningful improvement in OS versus placebo plus chemotherapy (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.53-0.93; 2-sided P = .0140). The median OS was 21.9 months (95% CI, 15.5-not evaluable) with cemiplimab plus chemotherapy and 13 months (95% CI, 11.9-16.1) with placebo plus chemotherapy. The median PFS was 8.2 months (95% CI, 6.4-9.3) in the cemiplimab arm versus 5 months (95% CI, 4.3-6.2) in the placebo arm (HR, 0.56; 95% CI, 0.44-0.70; P <.0001). The ORR was 43% (95% CI, 38-49) and 23% (95% CI, 16-30), respectively.
The most common (≥15%) adverse events in the study were alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite.