FDA Cancer Therapy Approvals in April and May 2021
In April and May 2021, the US Food and Drug Administration (FDA) granted approval for ten new indications for cancer treatments.
- Two New Options for Advanced Non-Small Cell Lung Cancer (NSCLC)
Amivantamab for EGFR Exon 20 Insertion-Mutant Advanced NSCLC. Accelerated approval was granted to amivantamab-vmjw (Rybrevant®, Janssen Biotech, Inc.), a novel, fully human EGFR-MET bispecific antibody with immune cell-directing activity that targets activating and resistance EGFR mutations, as well as MET mutations and amplifications. It was approved for the treatment of patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations – as detected by the simultaneously approved companion diagnostic, Guardant360®CDx – whose disease has progressed on or after platinum-based chemotherapy. The approval was based on results from the multicenter, open-label, multicohort phase I CHRYSALIS trial. Updated results reported an investigator-assessed overall response rate (ORR) of 40%, a clinical benefit rate of 74%, and median duration of response (DoR) of 11.1 months. Median progression-free survival (PFS) was 8.3 months, and median overall survival (OS) was 22.8 months.
Sotorasib for KRAS G12C Mutated NSCLC. Accelerated approval was granted to sotorasib (Lumakras™, Amgen Inc.), a RAS GTPase family inhibitor, for patients with KRAS G12C mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy. The companion diagnostics, QIAGEN therascreen® KRAS RGQ PCR kit (tissue) and the Guardant360®CDx (plasma) were simultaneously approved for detecting the mutation, either in plasma or in tumor tissue if the plasma test is negative. Results from the multicenter, single-arm, open-label, phase II CodeBreaK 100 trial supported the approval. Among 124 patients treated with sotorasib, the ORR was 37.1% (n=46) including three complete responses, and the median DoR was 10 months.
- Expanded Immune Checkpoint Inhibitor Indications in Gastric, Gastroesophageal Junction (GEJ), and Esophageal Cancers
Frontline Pembrolizumab Combination for Advanced HER2-Positive Gastric and GEJ Cancers. Accelerated approval was given to pembrolizumab (Keytruda®, Merck & Co.) in combination with trastuzumab, fluoropyrimidine-, and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma. Approval was based on the interim analysis of 264 patients in the ongoing double-blind, randomized, multicenter, phase III KEYNOTE-811 trial. Patients were randomized to receive pembrolizumab 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin. ORR per blinded independent central review (BICR) was 74% in the pembrolizumab arm compared with 52% in the placebo arm (P < 0.0001); the median DoR was 10.6 months versus 9.5 months, respectively.
Frontline Nivolumab Combination for Advanced HER2-Negative Gastric, GEJ and Esophageal Cancer. Nivolumab (Opdivo®, Bristol Myers Squibb Company) was granted approval in combination with fluoropyrimidine- and platinum- containing chemotherapy as first-line treatment for advanced or metastatic gastric, GEJ and esophageal cancer, based on the results from the randomized, multicenter, double-blind, phase III CheckMate-649 trial, which included 1,581 patients. Nivolumab plus chemotherapy resulted in a statistically significant improvement in OS and PFS versus chemotherapy alone in patients whose tumors expressed PD-L1 combined positive score (CPS) ≥5 (median OS: 14.4 versus 11.1 months; hazard ratio (HR), 0.71; P<0.0001; median PFS: 7.7 versus 6.0 months; HR, 0.88; P<0.0001). Median OS was also significantly improved in patients who had PD-L1 CPS ≥ 1 (14 versus 11.3 months; HR, 0.77; P=0.0001) and in all randomized patients (13.8 versus 11.6 months; HR, 0.80; P=0.0002).
Adjuvant Nivolumab for Resected Esophageal or GEJ Cancer. Nivolumab (Opdivo®, Bristol Myers Squibb Company) received approval for the treatment of patients with completely resected esophageal or GEJ cancer with residual pathologic disease who have received neoadjuvant chemoradiotherapy. In the randomized, multicenter, double-blind, phase III CheckMate-577 trial, a statistically significant improvement in median disease-free survival (DFS) was seen in patients treated with nivolumab (n=532) versus placebo (n=262): 22.4 months versus 11.0 months, respectively (HR, 0.69; P=0.0003). The DFS benefit was observed regardless of PD-L1 expression and histology.
- Two Indications for Antibody–Drug Conjugate, Sacituzumab Govitecan
Advanced Urothelial Cancer. Sacituzumab govitecan (Trodelvy®, Immunomedics Inc.) was granted accelerated approval for the treatment of patients with locally advanced or metastatic urothelial cancer, who have previously received a platinum-containing chemotherapy and either a PD-L1 or PD-1 inhibitor. Final results from cohort 1 (n=113) of the multicenter, open-label phase II TROPHY-U-01 trial showed an ORR of 27.7% with 5.4% complete responses. Median DoR was 5.9 months and clinical benefit rate (CBR) was 37%. Median OS was 10.5 months, and median PFS was 5.4 months.
Advanced Triple-Negative Breast Cancer (TNBC). Regular approval was given to sacituzumab govitecan for the treatment of patients with unresectable, locally advanced or metastatic TNBC following previous treatment with two or more systemic therapies, with at least one therapy for metastatic disease. The approval was granted based on the results from the multicenter, open-label, randomized, phase III ASCENT trial in which patients were randomized to receive either sacituzumab govitecan or physician’s choice of single-agent chemotherapy. In 468 patients with no brain metastases at baseline, sacituzumab govitecan significantly prolonged median PFS (5.6 versus 1.7 months; HR, 0.41; P<0.0001) and median OS (12.1 versus 6.7 months; HR 0.48; P<0.0001).
- Infigratinib, a FGFR-Selective Tyrosine Kinase Inhibitor, for Advanced Cholangiocarcinoma. Infigratinib (Truseltiq™, QED Therapeutics, Inc.) received accelerated approval for the treatment of patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth receptor 2 (FGFR2) fusion or rearrangement, as detected by the simultaneously approved companion diagnostic, FoundationOne®. Results from the multicenter, single arm, phase II BGJ398 study, in which 108 patients received infigratinib, showed an ORR of 23.1% (n=25), including one complete response; median DOR was 5.0 months. Among patients who responded to infigratinib treatment, 32.0% maintained their response for ≥6 months.
- Dostarlimab for Recurrent or Advanced Endometrial Cancer. Dostarlimab-gxly (Jemperli®, GlaxoSmithKline LLC), a programmed death receptor-1 (PD-1) inhibitor, gained accelerated approval for patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer – as determined by the simultaneously approved immunohistochemistry companion diagnostic, Ventana MMR RxDx Panel – that has progressed on or after prior platinum-containing chemotherapy. Updated results from the single-arm phase II GARNET trial, reported an ORR of 44.7% with complete response in 11.0% of patients. Median DoR or OS were not reached.
- Loncastuximab Tesirine for Relapsed or Refractory Large B-Cell Lymphoma. Accelerated approval was given to loncastuximab tesirine-lpyl (Zynlonta®, ADC Therapeutics SA), a CD19-directed antibody and alkylating agent conjugate for patients with relapsed or refractory large B‑cell lymphoma (after two or more lines of systemic therapy), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. The results of the single-arm, phase II LOTIS-2 trial supported the approval. Among 145 patients, the ORR was 48.3%, with half of the responding patients achieving complete response. After a median follow-up of 7.3 months, median DoR was 10.3 months.