FDA approves amivantamab with carboplatin and pemetrexed for NSCLC with EGFR exon 19 deletions or L858R mutations

• Efficacy from MARIPOSA-2 (NCT04988295), a randomized, open-label, multicenter trial in 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after receiving osimertinib.

• PFS (primary endpoint) by BICR was 6.3 months in the amivantamab + CP arm vs. 4.2 months in the CP arm (hazard ratio 0.48,  p-value<0.0001).

• At the prespecified second interim analysis of OS, with 85% of the deaths needed for the final analysis, there was no statistically significant difference in OS.

• Project Orbis countries included Australia, Canada and Brazil (all currently under review still).

FDA approves pembrolizumab with chemotherapy for unresectable advanced or metastatic malignant pleural mesothelioma

• Efficacy was investigated in KEYNOTE-483 (NCT02784171), a randomized, open-label trial in patients with unresectable advanced or metastatic MPM and no prior systemic therapy for advanced/metastatic disease

• The trial demonstrated a statistically significant improvement in OS for patients treated with pembrolizumab with chemotherapy vs. chemotherapy alone. Median OS was 17.3 months (95% CI: 14.4, 21.3) vs. 16.1 months (95% CI: 13.1, 18.2) (hazard ratio [HR] 0.79 [95% CI: 0.64, 0.98]; p=0.0162).

• Project Orbis review inc. the Australian TGA and Health Canada. The application reviews are ongoing at the other regulatory agencies.

FDA approves Kisqali with an aromatase inhibitor & Kisqali Femara Co-Pack for early high-risk breast cancer

• FDA approved Kisqali (ribociclib, Novartis) with an aromatase inhibitor for the adjuvant treatment of adults with HR-positive, HER2-negative stage II and III early breast cancer at high risk of recurrence.

• Efficacy of ribociclib with a non-steroidal aromatase inhibitor was evaluated in NATALEE (NCT03701334), a randomized, open-label, multicenter trial in 5101 adults with HR-positive, HER2-negative early breast cancer.

• Efficacy results at the final iDFS analysis showed that iDFS at 36 months was 90.7% (95% CI: 89.3, 91.8) in the ribociclib + NSAI arm and 87.6% (95% CI: 86.1, 88.9) in the NSAI arm, HR 0.749 (95% CI: 0.628, 0.892). At the time of the iDFS final analysis, OS was immature.

• Additionally, FDA also approved the ribociclib and letrozole co-pack for the same indication.

European Commission Approves Astellas’ PADCEV in Combination with KEYTRUDA for First-Line Treatment of Advanced Urothelial Cancer

• First regimen approved in advanced UC to demonstrate superiority to platinum-containing chemotherapy, the standard of care for nearly 40 years

• European MA based on positive overall survival and progression-free survival results from the global Phase 3 EV-302 trial

• median OS of 31.5 months compared to 16.1 months with platinum-containing chemotherapy, representing a 53% reduction in risk of death (Hazard Ratio [HR]=0.47; 95% Confidence Interval [CI]: 0.38-0.58; P<0.00001).

• PFS of 12.5 months for the combination compared to 6.3 months with chemotherapy represents a 55% reduction in the risk of cancer progression or death (HR=0.45; 95% CI: (0.38-0.54); P<0.00001)

Ordspono™ (odronextamab)R/R follicular lymphoma or R/R DLBCL, both 3rd Line

• First regulatory approval anywhere in the world for Regeneron’s CD20xCD3 bispecific antibody

• Approval based on results from the Phase 1 ELM-1 and pivotal Phase 2 ELM-2 trials, which demonstrated robust, durable response rates in adults with R/R FL or R/R DLBCL:

• In R/R FL, N=128, ORR was 80% (73% CR); median DoR in complete responders was 25 months

• In R/R DLBCL, N of 127, ORR was 52% (31% CR) in CAR-T therapy naive DoR for complete responders was 18months 

FDA Approves RYBREVANT (amivantamab) plus LAZCLUZE (lazertinib) in first-line chemotherapy-free treatment for patients with EGFR-mutated NSCLC

• Combination demonstrated a statistically significant improvement in PFS vs. osimertinib with a hazard ratio of 0.70; p-value=0.0002). The median PFS was 23.7 months vs. 16.6 months.

• No detriment was observed in OS.

• Project Orbis review inc. Australia, Brazil, Canada, Switzerland and the UK.

• Longer-term follow-up data from the Phase 3 MARIPOSA will be presented IASLC 2024 WCLC next month.

TEPKINLY® (epcoritamab) Receives Second European Commission Approval for the Treatment of Adults with r/r Follicular Lymphoma

• Conditional MA supported by Phase 1/2 EPCORE NHL-1: an open-label, multi-cohort, multicenter, single-arm trial in patients with R/R FL after two or more lines of prior systemic therapy. Patients included in the study were refractory to both anti-CD20 therapy and an alkylating agent.

• TEPKINLY (n=128) had an ORR of 83% and a CR rate of 63%. At a median follow-up of 16.2 months, the median duration of response was 21.4 months (13.7, NR). Duration of complete response (DOCR) was not reached.

• The safety profile of epcoritamab in the pivotal cohort was similar to the previously reported pivotal EPCORE NHL-1 DLBCL cohort (see link for details).

FDA approves neoadjuvant/adjuvant durvalumab for resectable non-small cell lung cancer

• Median EFS was not reached (95% CI: 31.9, not estimable [NE]) in the durvalumab arm and 25.9 months (95% CI: 18.9, NE) in the placebo arm (hazard ratio 0.68 [95% CI: 0.53, 0.88]; p-value=0.0039).

• pCR rate was 17% (95% CI: 13, 21) and 4.3% (95% CI: 2.5, 7) in the durvalumab and placebo arms, respectively.  

• At the time of the prespecified interim analyses, OS was not formally tested for statistical significance; however, a descriptive analysis revealed no clear detriment.