FDA approves osimertinib for locally advanced, unresectable (stage III) NSCLC following chemoradiation therapy

• Tagrisso (osimertinib, AstraZeneca), for adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

• Efficacy was evaluated in LAURA (NCT03521154), a double blind, randomized, placebo-controlled trial in 216 adult patients.

• Osimertinib demonstrated a statistically significant improvement in PFS vs. placebo with a hazard ratio of 0.16 (95% CI: 0.10, 0.24; p-value <0.001). The median PFS was 39.1 months (95% CI: 31.5, not estimable [NE]) in the osimertinib arm and 5.6 months (95% CI: 3.7, 7.4) in the placebo arm.

• While OS results were immature at the current analysis, with 36% of pre-specified deaths for the final analysis reported, no trend towards a detriment was observed.

FDA Approves Sanofi's Sarclisa in Newly Diagnosed Multiple Myeloma

• Sarclisa (isatuximab) with bortezomib, lenalidomide, and dexamethasone approved for NDMM adults who are not eligible for autologous stem cell transplant.

• Efficacy was evaluated in IMROZ (NCT03319667), an open-label, randomized, active-controlled phase 3 trial. Enrollment was limited to patients 80 years of age and younger. A total of 446 patients were randomized (3:2) to receive Isa-VRd or VRd.

• IMROZ demonstrated an improvement in PFS in the Isa-VRd arm with a 40% reduction in risk of disease progression or death (hazard ratio 0.60 [95% CI: 0.44, 0.81]; p-value 0.0009); the median PFS was not reached (NR) (95% CI: NR, NR) in the Isa-VRd arm and was 54.3 months (95% CI: 45.2, NR) in the VRd arm.

• The most common adverse reactions (≥20%) were upper respiratory tract infection, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19 infection

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.