Patritumab-Dx demonstrates a statistically significant Ph 3 PFS improvement in NSCLC

CLINICAL AND REGULATORY 

Patritumab deruxtecan demonstrates a statistically significant PFS improvement in NSCLC 

OS data were immature at the time of the analysis and the trial will continue to further assess OS, a secondary endpoint. NSCLC accounts for approximately 85% of all lung cancers worldwide with up to 70% of NSCLC cases diagnosed at an advanced stage and EGFR-activating mutations occur in 14% to 38% of all NSCLC tumors worldwide.1,2,3 Following initial treatment for metastatic EGFR-mutated NSCLC with an EGFR TKI, many patients experience disease progression and currently available therapies in the second-line setting are limited, highlighting the need for new approaches to improve outcomes. 

Ifinatamab deruxtecan continues to demonstrate promising ORR in SCLC patients in Phase 2 trial 

Results from an interim analysis of the dose-optimization part of the ongoing IDeate-Lung01 Phase 2 trial showed ifinatamab deruxtecan (I-DXd) continues to demonstrate promising objective response rates in patients with pretreated extensive-stage small cell lung cancer (ES-SCLC). These data were featured today as part of a press conference and were presented during an oral presentation at the 2024 World Conference on Lung Cancer. Ifinatamab deruxtecan is a specifically engineered potential first-in-class B7-H3 directed ADC discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and Merck & Co. A confirmed ORR of 54.8% and 26.1% were observed in patients with ES-SCLC receiving ifinatamab deruxtecan in the 12 mg/kg (n=42) and 8 mg/kg (n=46) cohorts, respectively. Twenty-three PR were seen in the 12 mg/kg cohort. One CR and eleven PRs were seen in the 8 mg/kg cohort. A median DoR of 4.2 months and 7.9 months and a DCR of 90.5% and 80.4% were observed in the 12 mg/kg and 8 mg/kg cohorts, respectively. The median duration of treatment was 4.7 months for the 12 mg/kg dose and 3.5 months for the 8 mg/kg dose. Median PFS of 5.5 months and 4.2 months and median OS of 11.8 months and 9.4 months were observed in the 12 mg/kg and 8 mg/kg cohorts, respectively. The 12 mg/kg dose has been selected for the dose expansion part of the trial. 

Rina-S shows promising anti-tumor activity as single agent in ovarian and endometrial cancers 

Genmab announced new data from the Phase 1/2 study of rinatabart sesutecan (Rina-S), an investigational FRα-targeted, Topo1 ADC, demonstrated a confirmed ORR of 50.0% (95% CI) in ovarian cancer patients treated with Rina-S 120 mg/m2 once every 3 weeks, regardless of FRα expression levels. These data were from the dose expansion part of a multi-part study evaluating the safety and efficacy of single-agent Rina-S in ovarian cancer and endometrial cancer. These results, and additional findings from the study, were presented at the ESMO Congress. Part B of the study randomized 42 previously treated patients with histologically or cytologically confirmed advanced OC (epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer) to Rina-S 100 mg/m2 (n=22) or Rina-S 120 mg/m2 (n=20). Ninety-five percent of patients in the 120 mg/m2 group were identified as platinum-resistant ovarian cancer (PROC) as were 90.9% of patients in the 100 mg/m2 group. In patients receiving Rina-S 100 mg/m2, results showed a confirmed ORR of 18.2% compared with 50.0% among patients receiving 120 mg/m2. Results for 100 mg/m2 and 120 mg/m2 respectively also included: complete response: 0 (0%) and 1 (5.6%); partial response in 4 (18.2%) and 8 patients (44.4%); stable disease in 15 (68.2%) and 7 patients (38.9%); disease progression in 3 patients (13.6%) and 1 patient (5.6%). Only one patient in the 120 mg/m2 treatment arm was not evaluable. With a median on study follow-up of 24 weeks, all confirmed responses with the 120 mg/m2 dose were ongoing at the time of data cutoff. The disease control rate (DCR) was 86.4% and 88.9% (95% CI: 65.3-98.6), respectively. 

Survival results for AZ/Daiichi’s datopotamab deruxtecan did not achieve statistical significance 

High-level results from the TROPION-Breast01 Phase 3 trial of datopotamab deruxtecan (Dato-DXd) compared to investigator’s choice of chemotherapy, which previously met the dual primary endpoint of PFS, did not achieve statistical significance in the final OS analysis in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. This analysis follows the positive PFS results presented at the 2023 ESMO Congress which showed datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS. An improvement in patient-reported outcomes was also seen.