FDA Approved 6 New Oncology Indications in December 2022

The US FDA approved six new indications for cancer management in December. This includes updated labeling for capecitabine tablets.

  • Oral Capecitabine Label Update. Updated labeling was approved for capecitabine tablets (Xeloda®, Genentech, Inc.) under Project Renewal, an Oncology Center of Excellence initiative. Capecitabine is the first drug to receive a labeling update under this pilot program, which reviews older, commonly-prescribed oncology drugs to ensure that the information is clinically meaningful and scientifically up-to-date. The label includes several new and revised indications for colorectal cancer, advanced or metastatic breast cancer, pancreatic adenocarcinoma, and unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer. Additional labeling revisions include updated dosages for several indications, including an optional lower starting dose for patients with metastatic breast cancer. Severe renal impairment is no longer a contraindication, and new information on exposure to crushed tablets has been added under Warnings and Precautions. Additional information on capecitabine use and dihydropyrimidine dehydrogenase (DPD) deficiency has also been provided.
  • Atezolizumab for Alveolar Soft Part Sarcoma (ASPS). Atezolizumab (Tecentriq®, Genentech, Inc.) received approval for adult and pediatric patients ≥ 2 years old with unresectable or metastatic ASPS following priority review and breakthrough designation. Results from the open-label, single-arm phase 2 Study ML39345 (NCT03141684) supported the approval. The trial evaluated the efficacy and safety of the PD-L1 blocking antibody atezolizumab in 49 patients ≥2 years old with histologically or cytologically confirmed ASPS that was not curable by surgery, and an ECOG performance status ≤2.The primary endpoints were overall response rate (ORR) and duration of response (DoR). The ORR was 24%. Among the 12 responders, all patients achieved a partial response. Two-thirds (67%) achieved a DoR of at least 6 months, and 42% achieved a DoR of at least 12 months. The recommended dosage for adult patients is 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks until disease progression or unacceptable toxicity. However, for pediatric patients ≥ 2 years old the dose is 15 mg/kg (up to a maximum of 1200 mg) every 3 weeks until disease progression or unacceptable toxicity.
  • Adagrasib for KRAS G12C-Mutated Non-Small Cell Lung Cancer (NSCLC). The RAS GTPase family inhibitor adagrasib (Krazati®, Mirati Therapeutics, Inc.) received accelerated approval for adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, who have received at least one prior systemic therapy. Two companion diagnostic tests were approved simultaneously, the QIAGEN therascreen KRAS RGQ PCR kit (tissue) and the Agilent Resolution ctDx FIRST Assay (plasma). The approval was based on results from KRYSTAL-1, a multicenter, single-arm, open-label clinical trial, which included 116 patients with locally advanced or metastatic NSCLC with confirmed KRAS G12C mutations. In a registrational phase 2 cohort, the confirmed ORR was 43% (48 of 112 patients who had measurable disease at baseline; 95% CI: 33.5, 52.6). The median DoR was 8.5 months (95% CI: 6.2, 13.8), and the median progression-free survival (PFS) was 6.5 months (95% CI: 4.7, 8.4). Among 33 patients with previously treated, stable central nervous system metastases, the confirmed intracranial ORR was 33.3%. A total of 52 patients (44.8%) had grade 3 or higher TRAEs; the most common were fatigue, nausea, increased ALT level (each in 4.3%), and increased AST level (3.4%). Two grade 5 fatal events (in 1.7% of the patients) were reported. TRAEs led to dose reduction in 60 patients (51.7%) and dose interruption in 71 patients (61.2%).
  • First Adenoviral Vector-Based Gene Therapy for BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). Approval was granted to nadofaragene firadenovec-vncg (Adstiladrin®, Ferring Pharmaceuticals) for adult patients with high-risk Bacillus Calmette-Guérin (BCG) unresponsive NMIBC with carcinoma in situ with or without papillary tumors. This is the first approval of an adenoviral vector-based gene therapy for this indication. The approval was based on efficacy data from Study CS-003 (NCT02773849), a multicenter, single-arm phase 3 trial. Of 157 enrolled patients with high-risk NMIBC, 98 had Bacillus Calmette-Guérin (BCG) unresponsive carcinoma in situ and were evaluable for response. Complete response (CR) and DoR were the major efficacy outcome measures. Investigators performed cystoscopy with transurethral resection of bladder tumor (TURBT) and biopsies and urine cytology to assess response; negative results were considered a CR. The CR rate was 51% and the median DoR was 9.7 months. Nearly half (46%) of responding patients maintained their CR for at least 12 months. Patients received nadofaragene firadenovec-vncg 75 mL intravesical instillation once every three months up to 12 months. Patients who did not develop a high-grade recurrence could continue to receive the therapy every three months.

  • Olutasidenib for Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML). Olutasidenib (Rezlidhia™, Rigel Pharmaceuticals, Inc.) was approved to treat adult patients with R/R AML with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation, as detected by a simultaneously approved FDA-approved test, the Abbott RealTime IDH1 Assay. This approval was based on results from Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, phase 2 multicenter registrational trial, which included 147 adult patients with R/R AML and confirmed IDH1 mutation. The median treatment duration was 4.7 months and 11% of patients underwent allogeneic transplant following treatment. The primary endpoint was  rate of CR plus CR with partial hematological recovery (CRh). The CR + CRh rate was 35% (n=51; 95% CI: 27.0, 43.0) and the median time to CR/CRh was 1.9 months (95% CI: 0.9, 5.6). The ORR was 48% (n=71; 95% CI: 40.0, 56.7). Response rates were similar for 12 patients who had received prior venetoclax. Median duration of CR/CRh was 25.9 months (95% CI: 10.6, NE). Median DOR was 11.7 months (95% CI: 6.9, 25.9). Median OS was 11.6 months (95% CI: 8.9, 15.5). Grade 3/4 TEAEs (≥10%) were febrile neutropenia and anemia (n=31; 20% each), thrombocytopenia (n=25; 16%) and neutropenia (n=20; 13%). The FDA recommends treatment for a minimum of 6 months for patients without disease progression or unacceptable toxicity to allow for clinical response.
  • Mosunetuzumab-axgb for R/R Follicular Lymphoma (FL). Accelerated approval was granted to the bispecific CD20-directed CD3 T-cell engager mosunetuzumab-axgb (Lunsumio™, Genentech, Inc.), for adult patients with R/R FL after ≥2 lines of systemic therapy. Efficacy was evaluated in GO29781 (NCT02500407), an open-label, multinational, multi-cohort phase 2 study. The efficacy population consisted of 90 patients with R/R FL who had received at least two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent. Centrally assessed ORR was the main efficacy outcome measure. The ORR was 80% (95% CI: 70, 88) and 60% of patients achieved CR. With a median follow-up of 14.9 months for responders, estimated median DoR was 22.8 months (95% CI: 10, not reached). Twelve-month and 18-month estimated DoR was 62% and 57%, respectively. The prescribing information has a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS). Warnings and precautions include neurologic toxicity, infections, cytopenias, and tumor flare. Among 218 patients who received mosunetuzumab-axgb at the recommended dose, CRS occurred in 39% of patients, neurologic toxicity in 39% (including ICANS in 1%), serious infections in 17%, and tumor flare in 4%. For CRS, Grade 2 occurred in 15%, Grade 3 in 2%, and Grade 4 in 0.5%.