Key Oncology Updates: Approvals, Designations, and Trial Results
核心洞察
Treosulfan gains FDA approval for allogeneic hematopoietic stem cell transplantation conditioning in AML and MDS, offering a new option for adult and pediatric patients.
The FDA grants priority review to RP1 plus nivolumab for advanced melanoma (搜索) after PD-1 inhibitor failure, with a decision expected by July 2025.
Dato-DXd receives breakthrough therapy designation from the FDA for pretreated EGFR (搜索)-mutated NSCLC, based on promising phase 2 and 3 trial data.
The oncology field has seen several significant developments, ranging from new drug approvals and designations to promising trial results that could reshape treatment paradigms. Here’s a roundup of the key updates.
Treosulfan Approved for HCT Conditioning in AML and MDS
The FDA has approved treosulfan (Grafapex) in combination with fludarabine as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in adult and pediatric patients (at least 1 year old) with acute myeloid leukemia (搜索) (AML) or myelodysplastic syndrome (搜索) (MDS). This decision was based on the phase 3 MC-FludT.14/L trial (NCT00822393). According to Filippo Milano, MD, PhD, of Fred Hutch Cancer Center, this approval provides a useful option for these patients, potentially improving overall survival while minimizing adverse effects.
Priority Review for RP1 Plus Nivolumab in Advanced Melanoma
The FDA has accepted and granted priority review to Replimune's biologics license application (BLA) for RP1 (vusolimogene oderparepvec) combined with nivolumab (Opdivo) for treating adult patients with advanced melanoma (搜索) who have previously progressed on a PD-1-containing regimen. The BLA is supported by data from the phase 1/2 IGNYTE trial (NCT03767348), presented at the 2024 SITC Annual Meeting. The target action date is set for July 22, 2025. Sushil Patel, PhD, of Replimune, expressed eagerness to collaborate with the FDA during the review process. The IGNYTE study (n = 140) showed a confirmed overall response rate of 33.6% (95% CI, 25.8%-42.0%) with the combination.
Dato-DXd Gains Breakthrough Therapy Designation for EGFR-Mutated NSCLC
The FDA has granted breakthrough therapy designation to datopotamab deruxtecan (Dato-DXd) for adult patients with locally advanced or metastatic, EGFR (搜索)-mutated non-small cell lung cancer (搜索) (NSCLC) who have progressed on or after treatment with an EGFR TKI and platinum-based chemotherapy. This decision is backed by findings from the phase 2 TROPION-Lung 05 (NCT04484142) and phase 3 TROPION-Lung01 (NCT04656652) trials. Pooled data from these trials (n = 117) showed an objective response rate of 42.7% (95% CI, 33.6%-52.2%) by blinded independent central review.
Encorafenib Combo Approved for BRAF V600E+ Metastatic CRC
The FDA has granted accelerated approval to encorafenib (Braftovi) combined with cetuximab (Erbitux) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) for metastatic colorectal cancer (搜索) (CRC) patients with a BRAF (搜索) V600E mutation, based on the phase 3 BREAKWATER study (NCT04607421). The combination (n = 110) showed an objective response rate (ORR) of 61% (95% CI, 52%-70%) compared to 40% (95% CI, 31%-49%) with chemotherapy with or without bevacizumab (Avastin; n = 110; P = .0008). The median duration of response was 13.9 months (95% CI, 8.5-NE) and 11.1 months (95% CI, 6.7-12.7), respectively.
Ensartinib Approved for ALK+ NSCLC
Ensartinib (Ensacove) has been approved by the FDA for adult patients with ALK (搜索)-positive locally advanced or metastatic non-small cell lung cancer (搜索) (NSCLC) who have not previously been treated with an ALK inhibitor. The phase 3 eXALT3 study (NCT02767804) demonstrated a median progression-free survival of 25.8 months (95% CI, 21.8-NE) with ensartinib versus 12.7 months (95% CI, 9.2-16.6) with crizotinib (Xalkori), representing a 44% reduction in disease progression or death risk (HR, 0.56; 95% CI, 0.40-0.79; P = .0007).
Amivantamab Plus Lazertinib Improves OS in EGFR-Mutant Advanced NSCLC
Frontline treatment with amivantamab-vmjw (Rybrevant) combined with lazertinib (Lazcluze) significantly improved overall survival compared to osimertinib (Tagrisso) monotherapy in patients with locally advanced or metastatic NSCLC harboring EGFR (搜索) exon 19 deletions or L858R substitution mutations, meeting the final prespecified secondary endpoint of the phase 3 MARIPOSA study (NCT04487080). According to Stephen Liu, MD, of Georgetown’s Lombardi Comprehensive Cancer Center, this OS increase reaffirms that first-line treatment with amivantamab and lazertinib can lead to better patient outcomes.
Iparomlimab/Tuvonralimab Plus Chemo Shows Responses in Recurrent/Metastatic Cervical Cancer
Updated findings from the phase 2 DUBHE-C-204 trial (NCT05179317) indicated that iparomlimab with tuvonralimab (QL1706) and chemotherapy plus or minus bevacizumab (Avastin) elicited a confirmed ORR of 75.9% (95% CI, 62.8%-86.1%) in the overall efficacy-evaluable population of patients with recurrent or metastatic cervical cancer (搜索) (n = 58) at a median follow-up of 27.0 months (range, 1.4-35.3).
Capivasertib Plus Abiraterone/ADT Improves rPFS in PTEN-Deficient mHSPC
The addition of capivasertib (Truqap) to abiraterone acetate (Zytiga) and androgen deprivation therapy (ADT) produced a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) vs placebo plus abiraterone and ADT in patients with PTEN (搜索)-deficient de novo metastatic hormone-sensitive prostate cancer (搜索) (mHSPC), meeting the primary end point of the phase 3 CAPItello-281 trial (NCT04493853).
Belantamab Mafodotin-Based Combos in R/R Myeloma
The FDA has accepted a biologics license application (BLA) seeking the approval of 2 belantamab mafodotin (Blenrep) in combination with bortezomib (Velcade) and dexamethasone (BVd) and in combination with pomalidomide (Pomalyst) and dexamethasone (BPd), for the treatment of patients with multiple myeloma (搜索) who have received at least 1 prior line of therapy. The FDA has set a target action date for the BLA of July 23, 2025, under the Prescription Drug User Fee Act.
These updates reflect ongoing efforts to improve treatment options and outcomes for patients across various cancer types.