FDA Approved 6 New Oncology Indications in August 2023
The US FDA approved six new indications for cancer management in August 2023. Of these approvals, two were for multiple myeloma. The remainder were for solid tumors of the lung, prostate, and colon. Additionally, one agent received approval for uveal melanoma.
- Trifluridine and Tipiracil for Metastatic Colorectal Cancer (mCRC). Trifluridine and tipiracil (LONSURF, Taiho Oncology, Inc.) received approval in combination with bevacizumab for mCRC previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy and an anti-VEGF biological therapy, and if RAS wild-type an anti-EGFR therapy. This is an update to the approval in 2015 of trifluridine/tipiracil monotherapy in this indication. Approval was based on safety and efficacy data from SUNLIGHT (NCT04737187), a randomized, open-label, global trial that compared trifluridine and tipiracil with and without bevacizumab in 492 patients with mCRC who had received up to two prior chemotherapy regimens and experienced progressive disease or intolerance to the last regimen. The primary outcomes were overall survival (OS) and progression-free survival (PFS). A statistically significant OS improvement was reported in patients who received the regimen plus bevacizumab compared with those who did not receive bevacizumab (Hazard Ratio [HR] 0.61; 95% Confidence Interval [CI], 0.49 to 0.77; 1-sided P < 0.001). Median OS was 10.8 months in the combined treatment arm (95% CI, 9.4 to 11.8) and 7.5 months in the trifluridine/tipiracil-only arm (95% CI, 6.3 to 8.6);median PFS was 5.6 months (95% CI, 4.5 to 5.9) and 2.4 months (95% CI, 2.1 to 3.2), respectively(HR was 0.44;95% CI, 0.36 to 0.54; 1-sided P < 0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported.
- Pralsetinib For Non-Small Cell Lung Cancer (NSCLC). The oral selective RET inhibitor pralsetinib (Gavreto, Genentech, Inc.) received regular approval for patients with metastatic RET fusion-positive NSCLC detected by an FDA-approved test. In 2020, pralsetinib received accelerated approval based on initial overall response rate (ORR) and duration of response (DOR) in 114 patients enrolled in ARROW (NCT03037385), a multicenter, open-label, multi-cohort trial. Additional data from 25 months of further follow up, and an additional 123 patients, resulted in the conversion to regular approval. Patients received pralsetinib until disease progression or unacceptable toxicity. As determined by a blinded independent review committee (BIRC), the ORR was 78% (95% CI, 68 to 85) among 107 treatment-naïve patients, with a median DOR of 13.4 months (95% CI, 9.4 to 23.1). Among 130 patients previously treated with platinum-based chemotherapy, the ORR was 63% (95% CI, 54 to 71) with a median DOR of 38.8 months (95% CI, 14.8 to not estimable). Adverse events experienced by at least 25% of subjects included musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough.
- Niraparib and Abiraterone Acetate for BRCA-mutated Metastatic Castration-Resistant Prostate Cancer (mCRPC). The fixed-dose combination of niraparib and abiraterone acetate (Akeega, Janssen Biotech, Inc.), with prednisone, received approval for patients with BRCA-mutated mCRPC, as determined by an FDA-approved test. This approval was based on efficacy data from Cohort 1 of MAGNITUDE (NCT03748641), a randomized double-blind, placebo-controlled, multicenter trial that studied homologous recombination repair (HRR) gene-mutated mCRPC. Patients received abiraterone acetate plus prednisone and were randomized to receive either niraparib or placebo. Of the 423 patients enrolled, 225 (53%) had BRCA gene mutations (BRCAm). The major efficacy outcome was radiographic progression-free survival (rPFS) per RECIST version 1.1 for soft tissue and Prostate Cancer Working Group 3 criteria for bone, assessed by BICR. OS was an additional endpoint. A statistically significant improvement in rPFS was seen in the niraparib group, with a median of 16.6 months vs 10.9 months in the placebo group (HR 0.53; 95% CI 0.36 to 0.79; P = 0.0014). In the BRCAm subgroup, an exploratory OS analysis revealed a median of 30.4 months in the niraparib arm vs 28.6 months in the standard of care arm (HR 0.79; 95% CI, 0.55 to 1.12). The overall Cohort 1 intention to treat (ITT) HRR population showed a statistically significant rPFS improvement (HR 0.73; 95% CI, 0.56 to 0.96; P = 0.0217). However, on further analysis, the subgroup of patients with BRCAm was primarily responsible for the improvement in the ITT HRR gene-mutated population. In Cohort 1, 27% of patients in the niraparib group required a blood transfusion, including 11% who required multiple transfusions. Laboratory anomalies were common, as were nausea, fatigue, and musculoskeletal pain.
- Melphalan for Uveal Melanoma. The HEPZATO KIT (melphalan for Injection/Hepatic Delivery System) containing melphalan (HEPZATO, Delcath Systems, Inc.) received approval as a liver-directed treatment for patients with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation. This combination product administers melphalan directly to the liver through a novel hepatic percutaneous perfusion delivery system into the hepatic artery, which permits higher drug exposure in target tissues. This approval was based on the single-arm, open-label, multicenter FOCUS study (NCT02678572), which included 91 patients with uveal melanoma with unresectable hepatic metastases. The main efficacy outcome measures were ORR and DOR as assessed by an independent central review committee using RECIST v1.1 criteria. The ORR was 36.3% (95% CI, 26.4 to 47) and the median DOR was 14 months (95% CI, 8.3 to 17.7). The prescribing information includes a Boxed Warning for severe peri-procedural complications, which can include hemorrhage, hepatocellular injury, and thromboembolic events. Additionally, a second Boxed Warning has also been issued for myelosuppression plus severe infection, bleeding, or symptomatic anemia. The melphalan delivery kit is available only through a restricted program under an FDA Risk Evaluation and Mitigation Strategy (REMS) called the HEPZATO KIT REMS.
- Talquetamab-tgvs for Relapsed or Refractory (R/R) Multiple Myeloma. The bispecific antibody Talquetamab-tgvs (Talvey, Janssen Biotech, Inc.) received accelerated approval for adults with R/R multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This accelerated approval was based on ORR and DOR data from MMY1001 (MonumenTAL-1) (NCT03399799, NCT4634552), as assessed by independent reviewers using International Myeloma Working Group (IMWG) criteria. Among 100 patients who received 0.4 mg/kg weekly, the ORR was 73% (95% CI, 63.2 to 81.4) and the median DOR was 9.5 months (95% CI, 6.5 to not estimable). Among 87 patients receiving 0.8 mg/kg biweekly, the ORR was 73.6% (95% CI, 63 to 82.4) and the median DOR was not estimable. The recommended dose is either 0.4mg/kg weekly or 0.8 mg/kg biweekly. Approximately 85% of responders maintained their response for at least 9 months. Among the safety population of 339 patients, the following adverse events occurred in 20% or more: CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea. Talquetamab’s prescribing information includes a Boxed Warning for life-threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Talquetamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli-Talvey REMS.
- Elranatamab-bcmm for R/R Multiple Myeloma. The bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, elranatamab-bcmm (Elrexfio, Pfizer, Inc.), received accelerated approval for adults with R/R multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This accelerated approval was based on ORR and DOR data from the open-label, single-arm, multicenter study MagnetisMM-3 (NCT04649359), which included patients refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody. Among 97 patients naïve to prior BCMA-directed therapy, BICR using IMWG criteria reported an ORR of 57.7% (95% CI, 47.3 to 67.7). With a median follow-up of 11.1 months among responders, the median DOR was not reached (95% CI, 12 months to not reached). The DOR rate at 6 months was 90.4% (95% CI, 78.4 to 95.9%) and at 9 months was 82.3% (95% CI, 67.1 to 90.9%). The most common adverse reactions (≥20%) were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets. Elranatamab’s prescribing information includes a Boxed Warning for life-threatening or fatal CRS and neurologic toxicity, including ICANS. Elranatamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the ELREXFIO REMS.