FDA Approved 6 New Oncology Indications in May-July 2023

The US FDA approved six new indications for cancer management in May-July 2023. Of these approvals, three were for hematologic malignancies, while two others address prostate cancer. Additionally, one agent received approval for endometrial cancer. 

  • Dostarlimab for Endometrial Cancer. Dostarlimab-gxly (Jemperli, GlaxoSmithKline) received approval when administered with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly. This indication is for primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H). Approval was based on efficacy data from RUBY (NCT03981796), a randomized, multicenter, double-blind, placebo-controlled trial. A pre-specified subgroup of 122 patients had dMMR/MSI-H primary advanced or recurrent endometrial cancer. In the overall dMMR/MSI-H population, investigators observed a median PFS of 30.3 versus 7.7 months (Hazard Ratio [HR] = 0.29; 95% Confidence Interval [CI], 0.17 to 0.50; P < 0.0001), for the dostarlimab-gxly and placebo regimens, respectively. Two-year PFS in the subgroup was 61.4% (95% CI, 46.3 to 73.4) in the dostarlimab group versus 15.7% (95% CI, 7.2 to 27.0) in the placebo group (HR for progression or death 0.28; 95% CI, 0.16 to 0.50; P < 0.001). The most common treatment-related adverse events were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%, respectively), and fatigue (51.9% and 54.5%, respectively).
  • Talazoparib with Enzalutamide for HRR Gene-Mutated Metastatic Castration-Resistant Prostate Cancer (mCRPC). Talazoparib (Talzenna, Pfizer, Inc.) received approval when used with enzalutamide for homologous recombination repair (HRR) mCRPC. This approval was based on efficacy data from TALAPRO-2 (NCT03395197), a randomized, double-blind, placebo-controlled, multi-cohort trial enrolling 399 patients with HRR gene-mutated mCRPC. Patients had either had a prior orchiectomy or received gonadotropin-releasing hormone analogs. Patients were randomized to either talazoparib or placebo; additionally, all patients received enzalutamide. At the planned primary analysis, the median follow-up for radiographic PFS was 24.9 months for the talazoparib group and 24.6 months for the placebo group. Among the HRR gene-mutated population, the median radiographic PFS was not reached in the talazoparib group, while the median was 13.8 months in the placebo group (HR 0.45; 95% CI, 0.33 to 0.61; < 0.0001). In patients with BRCA-mutated mCRPC (n=155), the HR for radiographic PFS was 0.20 (95% CI, 0.11 to 0.36). In patients with non-BRCAm HRR gene-mutated mCRPC, the HR for radiographic PFS was 0.72 (95% CI, 0.49 to 1.07). The most common grade 3–4 treatment-related adverse event was anemia (185 of 398 patients; 46%), which improved after dose reduction; only 33 patients (8%) discontinued talazoparib due to anemia.
  • Olaparib with Abiraterone and Prednisone for BRCA-mutated mCRPC. Olaparib (Lynparza, AstraZeneca Pharmaceuticals LP) received approval with abiraterone and prednisone (or prednisolone) for patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test. Efficacy data from the double-blind, phase III PROpel trial (NCT03732820) provided the basis for this approval. PROpel examined the combination of abiraterone and olaparib versus abiraterone and placebo in patients with mCRPC in the first-line setting. The investigators observed a statistically significant improvement in radiographic PFS for olaparib plus abiraterone compared with placebo plus abiraterone in the intent-to-treat (ITT) population. In the primary report, the 711 patients (89% of ITT population) without BRCAm, had a radiographic PFS HR of 0.77 (95% CI, 0.63 to 0.96) and the OS HR was 0.92 (95% CI, 0.74 to 1.14). The FDA found that the observed improvement in radiographic PFS in the ITT population may have been primarily attributable to patients with BRCAm. The median rPFS was not reached in the olaparib combination arm for the exploratory subgroup of 85 patients with BRCAm (11% of ITT population), compared to 8 months (95% CI, 6 to 15) in the control arm (HR 0.24; 95% CI, 0.12 to 0.45). The OS HR was 0.30 (95% CI, 0.15 to 0.59). In the final OS data analysis, investigators found that the olaparib combination prolonged OS by > 7 months vs standard-of-care abiraterone in the ITT population. The median OS of > 42 months is the longest median OS reported to date in a phase III trial in first-line mCRPC.
  • Quizartinib for Acute Myeloid Leukemia (AML). Quizartinib (Vanflyta, Daiichi Sankyo, Inc.) received approval for use with standard cytarabine and anthracycline induction and cytarabine consolidation, for the treatment of adult patients with newly diagnosed AML. Approval was also granted for quizartinib to be used as maintenance monotherapy following consolidation chemotherapy for newly diagnosed AML. An FDA-approved test must be used to confirm that the AML is FLT3 internal tandem duplication (ITD)-positive. FDA also approved LeukoStrat CDx FLT3 Mutation Assay as a companion diagnostic for quizartinib. FDA issued this approval based on efficacy data from the randomized, double-blind, placebo-controlled trial QuANTUM-First (NCT02668653). Patients were randomly assigned to receive quizartinib or placebo plus induction and consolidation therapy, followed by maintenance monotherapy according to their initial assignment. In the quizartinib group, median OS was 31.9 months vs 15.1 months in the placebo group (HR 0.78; 95% CI, 0.62 to 0.98; 2-sided = 0.0324). More than half the patients in each group (55%) achieved a complete response (CR), but the median duration was 38.6 months in the quizartinib group vs  12.4 months in the placebo group. Nearly all patients in both groups had at least one grade ≥ 3  adverse event (92% [n = 244] in the quizartinib vs 90% [n = 240] in the placebo group). The most common grade 3 or 4 adverse events were febrile neutropenia, hypokalemia, and pneumonia in both groups and neutropenia in the quizartinib group. A boxed warning for quizartinib notes QT prolongation, torsades de pointes, and cardiac arrest. Quizartinib is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Vanflyta REMS.
  • Glofitamab for Relapsed/Refractory (R/R) Large B-Cell Lymphomas. Glofitamab-gxbm (Columvi, Genentech, Inc.) received accelerated approval for R/R diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL) developing from follicular lymphoma, after two or more lines of systemic therapy. Approval for the bispecific CD20-directed CD3 T-cell engager glofitamab-gxbm was based on trial NP30179 (NCT03075696). The efficacy portion of this open-label, multicenter, single-arm Phase I/II trial included 132 patients, 80% of whom had R/R DLBCL, NOS and 20% had LBCL arising from follicular lymphoma. At a median follow-up of 12.6 months, 56% of the patients (95% CI, 47 to 65) had an objective response and 43% of the patients (95% CI, 35 to 52) had a complete response (CR). The estimated duration of response (DOR) among responders was 18.4 months (95% CI, 11.4 to not estimable) with a median follow-up of 11.6 months. The median time to response was 42 days. Among 145 patients in the safety cohort, cytokine release syndrome (CRS) occurred in 70% (Grade 3 or higher CRS, 4.1%), Immune Effector Cell-Associated Neurotoxicity (ICANS) in 4.8%, serious infections in 16%, and tumor flare in 12%. The prescribing information includes a Boxed Warning for serious or fatal CRS. Other Warnings and Precautions include neurologic toxicity such as ICANS, serious infections, and tumor flare. 
  • Epcoritamab for R/R DLBCL and high-grade B-cell lymphoma. Epcoritamab-bysp (Epkinly, Genmab US, Inc.) received accelerated approval for R/R DLBCL, NOS, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy. Efficacy data from EPCORE NHL-1 (NCT03625037), an open-label, multi-cohort, multicenter, single-arm trial in patients with R/R B-cell lymphoma, was used in this approval. The efficacy population consisted of 148 patients with R/R DLBCL, NOS, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy, including at least one anti-CD20 monoclonal antibody-containing therapy. In the primary publication, the overall response rate was 63.1% (95% CI, 55.0 to 70.6) and the complete response rate was 38.9% (95% CI, 31.2 to 46.9). The median DOR was 12.0 months (among complete responders: not reached). Updated data show with longer follow-up include an ORR of 63.1%, CR rates were 39.5% and were consistent for DLBCL (61.9% and 39.6%). The median duration of CR was 20.8 months, and the median time to CR was 2.7 months. CRS occurred in 51% of patients, ICANS in 6%, and serious infections in 15%. The prescribing information has a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS) and life-threatening or fatal immune effector cell-associated neurotoxicity syndrome (ICANS).