AiomNews N. 985, 14 Gennaio 2025

Oggi in Oncologia

Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial

Purpose: This phase II study evaluated the efficacy and tolerability of onvansertib, a polo-like kinase 1 (PLK1) inhibitor, in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) + bevacizumab for the second-line treatment of KRAS-mutant metastatic colorectal cancer (mCRC). … (leggi tutto)

Nel trattamento di seconda linea del carcinoma colorettale metastatico (mCRC) con mutazioni oncogeniche di KRAS, l’aggiunta di farmaci antiangiogenici alla chemioterapia ha mostrato benefici limitati, con un tasso di risposta compreso tra il 5% e il 23% e una sopravvivenza libera da progressione di circa 6-7 mesi.
In questo studio di fase Ib/II, open-label, a braccio singolo e multicentrico, Ahn et al. hanno valutato l’efficacia e la tollerabilità di onvansertib, un inibitore selettivo della polo-like chinasi 1 (PLK1), in combinazione con FOLFIRI e bevacizumab, come trattamento di seconda linea in questa popolazione di pazienti. PLK1 è una chinasi serina/treonina che regola il ciclo cellulare, controllandone l’ingresso e la progressione mitotica. Studi preclinici hanno suggerito che onvansertib, attraverso l’inibizione selettiva di PLK1, possa ridurre l’espressione di HIF1α e inibire la via dell’ipossia, potenziando così l’efficacia antitumorale di bevacizumab. Inoltre, in modelli di carcinoma colorettale è stata osservata una letalità sintetica tra l’inibizione di PLK1 e la mutazione di KRAS, suggerendo un potenziale terapeutico migliorato nei pazienti con questa mutazione.
Lo studio ha incluso 53 pazienti con mCRC KRAS-mutato in progressione dopo il trattamento di prima linea. L’endpoint primario era il tasso di risposta obiettiva (ORR), mentre gli endpoint secondari comprendevano la sopravvivenza libera da progressione (PFS) e la durata della risposta (DOR).
I risultati hanno evidenziato un ORR complessivo del 26,4%, non raggiungendo l’endpoint primario del 30%. Tuttavia, è emerso un miglioramento significativo nei pazienti naïve al trattamento con bevacizumab, in cui l’ORR ha raggiunto il 76,9%. La PFS mediana è stata di 8,4 mesi nella coorte complessiva, ma si è prolungata fino a 14,9 mesi nei pazienti non precedentemente esposti a bevacizumab. La durata mediana della risposta è risultata pari a 11,7 mesi, indicando un beneficio terapeutico prolungato. Precedenti regimi di seconda linea, come FOLFOX + bevacizumab o FOLFIRI + aflibercept, avevano mostrato nei pazienti naïve a bevacizumab un’ORR di circa il 20% e una PFS mediana di circa 7 mesi. Pertanto, i dati di questo studio suggeriscono che l’efficacia osservata nei pazienti naïve a bevacizumab potrebbe essere attribuita all’aggiunta di onvansertib. Inoltre, analisi precliniche indicano che l’esposizione pregressa a bevacizumab potrebbe indurre meccanismi di resistenza che limitano l’efficacia di onvansertib.
Sul fronte della sicurezza, il trattamento ha mostrato un profilo di tollerabilità accettabile e non sono state riscontrate tossicità vascolari rilevanti legate a bevacizumab, né interazioni inattese con onvansertib.
In conclusione, sebbene l’endpoint primario non sia stato raggiunto, l’aggiunta di onvansertib al trattamento con FOLFIRI e bevacizumab si presenta come un’opzione terapeutica sicura e potenzialmente promettente per i pazienti con mCRC KRAS-mutato naïve a bevacizumab. Tuttavia, si tratta di uno studio a braccio singolo, non randomizzato e interrotto prematuramente prima di raggiungere la dimensione campionaria prevista, comportando una ridotta potenza statistica. Inoltre, il maggiore beneficio clinico riscontrato nei pazienti naïve a bevacizumab deriva da un’analisi post hoc su un sottogruppo di pazienti, sottolineando l’importanza di ulteriori conferme attraverso studi più ampi e randomizzati.
Considerando che l’assenza di resistenza pregressa potrebbe massimizzare i benefici clinici dell’aggiunta dell’onvansertib, è attualmente in corso uno studio di fase II, open-label, multicentrico e randomizzato volto a valutare l’efficacia di questa combinazione come trattamento di prima linea, di cui attendiamo i risultati con interesse.

Omission of Surgical Axillary Staging Noninferior To Sentinel Lymph Node Biopsy in Patients with cN0, T1 or T2 Invasive Breast Cancer

Jan 13, 2025 – In a prospective, randomised, noninferiority Intergroup Sentinel Mamma (INSEMA) study that involved patients with early-stage, clinically node-negative (cN0), T1 or T2 invasive breast cancer (90% of whom had clinical T1 cancer), omission of surgical axillary staging was noninferior to sentinel lymph node biopsy after a median follow-up of approximately 6 years … (leggi tutto)

Adding Blinatumomab to Chemotherapy Improves DFS in Patients with Newly Diagnosed Childhood Standard-Risk B-Cell ALL of Average or High Risk of Relapse

Jan 13, 2025 – In an international, randomised, controlled, phase III AALL1731 study conducted by the Children’s Oncology Group (COG) involving children with standard-risk B-cell acute lymphoblastic leukaemia (ALL), the addition of blinatumomab to standard chemotherapy resulted in a significant improvement in disease-free survival (DFS) over chemotherapy alone … (leggi tutto)

FDA Grants Accelerated Approval to Zenocutuzumab-zbco for Non-Small Cell Lung Cancer and Pancreatic Adenocarcinoma

Jan 10, 2025 – On 4 December 2024, the US Food and Drug Administration (FDA) granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for adults with: advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) harbouring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy, or … (leggi tutto)

Jan 10, 2025 – MA is ready to support the implementation of the new regulation on health technology assessment (HTAR) (Regulation (EU) 2021/2282) when it becomes applicable on 12 January 2025. The regulation is an important step forward in accelerating and widening access to new medicines. In the European Union (EU), a centrally authorised medicine is accessible to patients when it has first gone through … (leggi tutto)

EMA Recommends Extension of Therapeutic Indications for Nivolumab and Ipilimumab

Jan 09, 2025 – On 14 November 2024, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted positive opinions, recommending a change to the terms of the marketing authorisation for the medicinal products nivolumab (Opdivo) and ipilimumab (Yervoy). The marketing authorisation holder for these medicinal products is Bristol-Myers Squibb Pharma EEIG. The CHMP adopted a new indication as follows (new indication in bold): … (leggi tutto)

Active Monitoring Promising for Women with Low-Risk Ductal Carcinoma In Situ

Jan 08, 2025 – In an intention-to-treat (ITT) analysis of the prospective, randomised non-inferiority COMET study, the 2-year cumulative rate of invasive cancer was 5.9% for women with low-risk ductal carcinoma in situ (DCIS) randomised to guideline-concordant care and 4.2% for active monitoring. These results show that at 2 years, patients randomised to active monitoring have non-inferior invasive breast cancer risk in the affected breast compared with those randomised … (leggi tutto)

Jan 13, 2025 – Dato-DXd has received FDA priority review for EGFR-mutated NSCLC, with a decision expected by July 2025.
Clinical trials showed a 42.7% objective response rate and a median progression-free survival of 5.8 months for Dato-DXd.
The safety profile of Dato-DXd was consistent, with no grade 4 or 5 treatment-related adverse effects reported ... (leggi tutto)

Jan 11, 2025 – Sunvozertinib shows promising ORR in NSCLC with EGFR exon 20 mutations, leading to FDA priority review.
Amivantamab and lazertinib improve overall survival in EGFR-mutant NSCLC, surpassing osimertinib.
FDA draft guidance outlines requirements for confirmatory trials in accelerated approval processes ... (leggi tutto)

Abenacianine Wins FDA Fast Track Designation for Tumor Visualization in the Lung

Jan 10, 2025 – Abenacianine (VGT-309) received FDA fast track designation to improve intraoperative visualization of lung cancer and related lesions.
Phase 2 trials showed abenacianine effectively visualizes lung tumors with a favorable safety profile, lacking serious adverse effects.
Primary endpoint of the study was clinically significant events post-imaging, with secondary endpoints assessing sensitivity, specificity, and ... (leggi tutto)

Jan 10, 2025 – Today, the U.S. Food and Drug Administration is providing an at-a-glance summary of news from around the agency: Today the FDA released a Long-Term National Strategy to Increase the Resiliency of the U.S. Infant Formula Market. The strategy builds on the Immediate National Strategy to Increase the Resiliency of the U.S. Infant Formula MarketExternal Link ... (leggi tutto)

BBO-8520 Receives FDA Fast Track Designation in KRAS G12C–Mutated Metastatic NSCLC

Jan 10, 2025 – BBO-8520 has received FDA fast track designation for KRAS G12C–mutated metastatic NSCLC, indicating its potential to address unmet medical needs.
The phase 1 trial evaluates BBO-8520’s safety, tolerability, and pharmacokinetics in KRAS G12C–mutated NSCLC and CRC patients.
The trial includes dose escalation and expansion phases, with BBO-8520 administered alone and with pembrolizumab. ... (leggi tutto)

GSK’227 Earns FDA Breakthrough Therapy Designation for Late-Line R/R Osteosarcoma

Jan 10, 2025 – GSK5764227 (GSK’227) received FDA breakthrough therapy designation for relapsed/refractory osteosarcoma after two prior therapies.
Phase 2 ARTEMIS-002 trial showed a 10.5% overall response rate and 78.9% disease control rate in osteosarcoma patients.
GSK’227 demonstrated higher efficacy at a 12.0 mg/kg dose compared to 8.0 mg/kg in the trial ... (leggi tutto)

Jan 09, 2025 – Amezalpat received orphan drug designation for HCC, showing significant survival benefits in the MORPHEUS-LIVER trial.
The trial demonstrated a six-month improvement in median overall survival with amezalpat, achieving 21 months vs 15 months in the control group.
Amezalpat’s objective response rate was 30%, compared to 13.3% in the control arm, with preserved benefits in key subgroups. ... (leggi tutto)

Jan 08, 2025 – The FDA’s draft guidance addresses tissue biopsies in clinical trials, emphasizing purpose, necessity, and risk considerations for adults and children.
High-risk biopsy sites require alternative approaches and strong scientific justification for inclusion in trials. Early discussions with review divisions and clear scientific rationale for biopsies are encouraged to enhance trial design. ... (leggi tutto)

Jan 08, 2025 – Invikafusp alfa (STAR0602) received FDA fast track designation for high TMB colorectal cancer, showing promise in addressing unmet oncology needs.
The phase 1/2 START-001 trial reported a 50% disease control rate and partial responses at optimal doses of 0.08 mg/kg and 0.12 mg/kg.
The trial included heavily pretreated patients resistant to anti–PD-(L)1 therapy, with a focus on safety, tolerability, and preliminary antitumor activity. ... (leggi tutto)

FDA Issues Draft Guidance for Accelerated Approval Confirmatory Clinical Trials

Jan 08, 2025 – The FDA’s draft guidance outlines criteria for confirmatory trials to be considered underway for accelerated approval, focusing on timelines, sponsor progress, and trial enrollment.
Amendments to the FD&C Act grant the FDA authority to ensure timely completion of confirmatory trials, requiring ... (leggi tutto)

Sunvozertinib Under FDA Priority Review for NSCLC With EGFR Exon 20 Insertion Mutations

Jan 07, 2025 – Sunvozertinib targets NSCLC with EGFR exon 20 insertion mutations, showing a 53.3% ORR in the WU-KONG1 Part B trial.
The drug demonstrated efficacy regardless of prior amivantamab exposure, with a 9-month DOR rate of 57%.
Common grade 3 or higher TRAEs included diarrhea and increased creatinine phosphokinase levels, but were mostly manageable ... (leggi tutto)

Jan 07, 2025 – Today, the U.S. Food and Drug Administration is providing an at-a-glance summary of news from around the agency: Today, the FDA posted warning letters sent to six firms selling unapproved drugs that claim to treat and control seizures in dogs and cats. The companies that received warning letters include Nutrition Strength Ltd. EOOD ... (leggi tutto)

Jan 09, 2025 – For patients under 70 with glioblastoma (GBM), the standard treatment combines radiotherapy (RT) with temozolomide (TMZ); however, the effectiveness of TMZ heavily depends on whether the MGMT promoter (MGMTp) is methylated. Although most patients with unmethylated MGMTp may not benefit significantly from TMZ, several trials have suggested a small survival benefit … (leggi tutto)

Jan 09, 2025 – Ancillary educational events are hosted independently by other Continuing Education-accredited providers and are held adjunct to the ASCO Gastrointestinal (GI) Cancers Symposium. They are not official events of the 2025 ASCO Gastrointestinal Cancers Symposium and are not sponsored, endorsed, or accredited by ASCO, Association for Clinical Oncology, or Conquer Cancer®, the ASCO Foundation … (leggi tutto)

Is There a Benefit to Switching First-Line Therapy Early Based on ctDNA Dynamics in HR-Positive, HER2-Negative Metastatic Breast Cancer?

Jan 08, 2025 – The treatment landscape for hormone receptor (HR)-positive HER2-negative metastatic breast cancer (MBC) has significantly changed over the last 5 years with the recent approvals of biomarker-guided therapies, and liquid biopsies have emerged as a practical and valuable diagnostic tool. A key question is whether using circulating tumor DNA (ctDNA) to make early switches in systemic therapy prior to clinical and/or radiographic progression improves clinical … (leggi tutto)

What Do Recent Clinical Trials Reveal About Biomarkers for Adjuvant Treatment in Localized RCC, and What’s Still Missing?

Jan 08, 2025 – Among patients with high-risk localized renal cell carcinoma, recurrence rates range from 40% to 50% after partial or radical nephrectomy, establishing a critical need for predictive biomarkers to guide adjuvant approaches. Certain existing biomarkers show predictive potential, but more studies are needed to determine how to implement them to guide intensity of surveillance after surgery and select those at the highest risk of recurrence for adjuvant treatment … (leggi tutto)

MECCA: Metronomic Chemotherapy Added to Endocrine Therapy Yields Improved Survival Outcomes in Some Patients With Metastatic Breast Cancer

Jan 08, 2025 – Metronomic chemotherapy has shown promise regarding efficacy and reduced toxicity among patients with breast cancer when combined with endocrine therapy, is unique in inhibiting angiogenesis, and modifies the tumor microenvironment and induces cell death. The MECCA trial showed that metronomic chemotherapy along with endocrine therapy yields improved progression-free … (leggi tutto)

Updated Guidelines for Pleural Mesothelioma Highlight New Treatments and Germline Testing

Jan 08, 2025 – The updated guidelines for the treatment of pleural mesothelioma (PM) emphasize a reduced role for surgery, new immunotherapy options, and universal germline testing. Doublet immunotherapy is now the preferred treatment option for patients with non-epithelioid disease, whereas chemotherapy, immunotherapy, or chemoimmunotherapy may be considered for patients with epithelioid disease, depending on patient goals and comorbidities. … (leggi tutto)

Pillole dall’AIFA

13 gennaio 2025 – Nota Informativa Importante su Veoza (fezolinetant)
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13 gennaio 2025 – Elenco dei farmaci innovativi: AIFA pubblica l’aggiornamento fino al 31 dicembre 2024
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10 gennaio 2025 – Aggiornamento “Diario di bordo sulla Trasparenza”
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10 gennaio 2025 – Ordine del giorno riunione Commissione Scientifica e Economica del Farmaco (CSE)
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09 gennaio 2025 – Notifica dei provvedimenti – Ufficio Ispezioni e Autorizzazioni GMP Medicinali
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09 gennaio 2025 – Richieste di audizioni presso la CSE AIFA
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07 gennaio 2025 – Tabelle farmaci di classe A e H al 17/06/2024
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