New Drug Approvals in Oncology: July-August 2023 Overview

Clinical Data:The approval of this indication is based on the results of a pivotal Phase II registrational clinical study (NCT03972722). The data from this Phase II clinical study have been presented by Professor Xiaohua Wu's team at several internationally renowned academic conferences, including an e-poster presentation at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in 2022, an e-poster presentation at the ESMO Immuno-Oncology (ESMO IO) Congress 2022, and an oral presentation at the ESMO Asia 2022 Congress.

According to the research results disclosed in the Yuheng Biotech press release in March 2023, as of April 29, 2022, in the full analysis set,Single-agent Treatment with Saipali Monoclonal AntibodyThe objective response rate (ORR) reached 27.8%, with 5 patients achieving complete response (CR) and 20 achieving partial response (PR); the median overall survival (OS) reached 16.8 months.The median duration of response (DoR) has not yet been reached. Additionally, zimberelimab has demonstrated long-term efficacy and a high objective response rate, with good safety.

Public Research Information of Sepulmonab

Clinical Data:This approval was based on the positive results of the DESTINY-Breast04 Phase III clinical trial, a global, randomized, open-label, registration study. This research is the first clinical trial targeting patients with HER2-low metastatic breast cancer, enrolling patients with HER2-low, inoperable, and/or metastatic breast cancer who had previously received 1-2 lines of chemotherapy. Patients were randomly assigned at a 2:1 ratio to either the trastuzumab deruxtecan group or the chemotherapy group. The results showed,In the HR-positive population, the progression-free survival (PFS) was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the chemotherapy group; in the overall population, the PFS was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the chemotherapy group. Regarding overall survival (OS), in the HR-positive population, the OS was 23.9 months in the trastuzumab deruxtecan group and 17.5 months in the chemotherapy group; in the overall population, the OS was 23.4 months in the trastuzumab deruxtecan group and 16.8 months in the chemotherapy group.

DESTINY-Breast04 Clinical Trial OS Data

Clinical Data:This approval is based on the QuANTUM-First study data presented at the 2022 EHA Congress. QuANTUM-First is a randomized, double-blind, placebo-controlled Phase III study designed to evaluate the overall survival (OS) improvement of Quizartinib in newly diagnosed FLT3-ITD positive AML adult patients. Patients were randomly assigned 1:1 to receive either Quizartinib or placebo in combination with standard cytarabine plus anthracycline induction therapy and cytarabine consolidation therapy, followed by single-agent maintenance therapy. The primary endpoint of the study is OS, with secondary endpoints including event-free survival (EFS), complete remission (CR) after induction, and composite CR.

The results showed,At a median follow-up of 39.2 months, the median OS in the Quizartinib group was 31.9 months, compared to 15.1 months in the placebo group.This indicates that Quizartinib combined with chemotherapy has achieved significant OS benefits in adult AML patients carrying FLT3-ITD mutations.

QuANTUM-First Clinical Trial OS Data

Clinical Data：The approval was mainly based on the interim analysis results of the Phase III RUBY study (NCT03981796). The results showed that, within a median follow-up time of over 25 months, the trial met the primary endpoint of investigator-assessed PFS.Patients with dMMR/MSI-H who received Dostarlimab-gxly combination therapy had a median PFS of 30.3 months, compared to 7.7 months in the control group.The results showed that the PFS of dMMR/MSI-H patients treated with Dostarlimab-gxly in combination with carboplatin and paclitaxel was prolonged in both statistically significant and clinically meaningful terms. Moreover, the risk of disease progression or death was reduced by 71% after treatment. Overall survival (OS) in the intent-to-treat (ITT) population, another co-primary endpoint of the study, is currently under evaluation.

RUBY Study Clinical Data

Clinical Data：The ARROW trial enrolled a total of 237 patients with locally advanced or metastatic RET fusion-positive NSCLC. All patients received pralsetinib treatment until disease progression or the occurrence of unacceptable toxicity.In 107 treatment-naïve patients, the ORR was 78%, with a median DoR of 13.4 months. In 130 patients previously treated with platinum-based chemotherapy, the ORR was 63%, with a median DoR of 38.8 months.

Clinical Data of Patients Previously Treated with Platinum-Based Chemotherapy in the ARROW Trial

In addition, the study enrolled 68 patients with advanced RET fusion-positive NSCLC from 10 medical centers in China. The results showed that pralsetinib provided durable clinical benefits in Chinese patients with RET fusion-positive advanced NSCLC, regardless of prior treatment, with higher response rates observed in treatment-naïve patients. Clinical data demonstrated that in patients previously treated with platinum-based chemotherapy, the confirmed ORR was 66.7%, including 1 CR and 21 PRs, with a disease control rate (DCR) of 93.9%. In patients who had not received prior systemic treatment, the confirmed ORR was 83.3%, including 2 CRs and 23 PRs, with a DCR of 86.7%.

Clinical Data：This approval is based on the Phase I/II clinical study of MonumenTAL-1, which enrolled patients (n=187) who had previously received at least four lines of therapy and had not been previously treated with T-cell redirection therapy, demonstrating a meaningful ORR.At a biweekly subcutaneous (SC) injection dose of 0.8 mg/kg, 73.6% of patients achieved ORR. At a weekly SC dose of 0.4 mg/kg, 73.0% of patients achieved ORR.

MonumenTAL-1 Trial Clinical Data (0.4 mg/kg SC Weekly Dose)

The MonumenTAL-1 study also enrolled 32 patients who were previously exposed to bispecific antibodies or CAR-T cell therapy (94% received B-cell maturation antigen (BCMA)-targeted therapy) and had undergone at least four prior lines of therapy (including proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies). These patients received Talquetamab-tgvs 0.4 mg/kg SC once weekly. With a median follow-up of 10.4 months, 72% of patients achieved an overall response rate (ORR) according to the assessment by the independent review committee, and it was estimated that 59% of responders maintained their response for at least 9 months.

Clinical Data：This approval is based on the results of the Phase III MAGNITUDE study. MAGNITUDE is a randomized, double-blind, placebo-controlled Phase III clinical trial designed to evaluate the efficacy and safety of niraparib in combination with abiraterone acetate and prednisone (AAP) versus placebo plus AAP as first-line treatment in patients with mCRPC with or without homologous recombination repair (HRR) gene mutations. The trial enrolled 423 patients (including 225 patients with BRCA mutations), with radiographic progression-free survival (rPFS) as the primary endpoint.

The results showed,In BRCA-mutated patients, niraparib + AAP significantly improved rPFS compared to placebo + AAP, with median rPFS of 16.6 months and 10.9 months in the two groups, respectively.Moreover, in patients with BRCA mutations, the median OS of patients in the Niraparib + AAP group showed a more favorable trend of improvement, with median OS values of 30.4 months and 28.6 months for the two groups, respectively.

MAGNITUDE Trial Clinical Data

Clinical Data：Elranatamab-bcmm is a humanized bispecific antibody that can simultaneously target MM cells expressing BCMA and T cells expressing CD3. This approval is based on the positive data from Cohort A of the MagnetisMM-3 (NCT04649359) study. The study is an open-label, multicenter, single-arm Phase II trial designed to evaluate the safety and efficacy of Elranatamab-bcmm monotherapy in patients with R/R MM. Cohort A enrolled 123 patients with R/R MM who were resistant to at least one proteasome inhibitor (PI), one immunomodulatory drug (IMiD), and one anti-CD38 monoclonal antibody.

The long-term efficacy data of Cohort A (n=123) presented at the 2023 European Hematology Association meeting showed that, at a median follow-up of 10.4 months,Patients receiving Elranatamab-bcmm as their first BCMA-targeted therapy achieved an ORR of 61%, with over 56.1% reaching a very good partial response rate (VGPR).With a median follow-up of 14.7 months, the median DoR, PFS, and OS were not reached. The probability of maintaining a response at 15 months for patients who achieved a response was 72%. Additionally, Elranatamab-bcmm demonstrated a manageable safety profile in the study.

MagnetisMM-3 Trial Clinical Data

Clinical Data：Dizal’s Sunvozertinib is a highly selective EGFR-targeted drug for various EGFR mutation subtypes. This approval is mainly based on the China registration clinical trial (WU-KONG6), a single-arm, multicenter Phase II registration study targeting patients with advanced NSCLC harboring EGFR exon20 insertions who have progressed on or are intolerant to platinum-based chemotherapy. The primary endpoint was the ORR assessed by the Independent Review Committee (IRC). The study results were presented as an oral report at the 2023 ASCO Annual Meeting.

In the efficacy analysis population of 97 patients treated with Dizal's drug,ORR Confirmed by IRC Reached 60.8%, more than 90% of patients experienced shrinkage of target lesions after single-agent treatment with Dizal’s drug.DCR Reached 87.6%As of the data cutoff date, 64.4% (38/59) of patients remained in ongoing response, with the duration of response (DoR) not yet reached, and the longest DoR exceeding 11.2 months. The safety profile was similar to that of traditional EGFR-TKIs, with good overall tolerability and manageable, reversible clinical adverse effects. With its high efficacy and low toxicity, Dizal’s Sunvozertinib has the potential to become a better treatment option for patients with EGFR exon20 insertion-mutated advanced non-small cell lung cancer (NSCLC).

Antitumor Efficacy of Sunvozertinib Assessed by IRC