Editor’s Note: Cell Cycle–Dependent and Schedule-Dependent Antitumor Effects of Sorafenib Combined with Radiation

Cancer Research · 2026-03-16

Supplementary Table 2 from Ipatasertib in Patients with Tumors with <i>AKT</i> Mutations: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1K

2025-12-01

<p>Supplementary Table 2. Genomic alterations identified and confirmed by the NCI-MATCH central assay.</p>

Real‐World Outcomes of Adjuvant Therapy in Stage III Melanoma and the Impact of Somatic Mutations

Cancer Medicine · 2025-12-01 · 1 citations

PURPOSE: A significant proportion of patients with locoregional (stage III) cutaneous melanoma recur despite adjuvant systemic therapy. Staging criteria and surgical nodal management have changed since the trials were completed. Data assessing the effect of systemic therapy compared to surveillance are limited, and factors associated with recurrence are unclear. We assessed the efficacy of adjuvant systemic therapy in real-world patients and assessed whether baseline genomic characteristics could prognosticate or predict benefit from therapy. METHODS: We collected demographic, histopathologic, clinical, and genomic data for patients diagnosed with stage III cutaneous melanoma. Outcomes of interest were recurrence-free survival (RFS) and distant-metastasis-free survival (DMFS). Survival analysis was performed using the Kaplan-Meier method with log-rank analysis. Univariate and multivariate analyses were performed using a Cox regression analysis. RESULTS: Two hundred and fifteen patients were included, of which 65 and 76 were treated with BRAF/MEK inhibitors (BRAFi/MEKi) and anti-PD1 adjuvant systemic therapy respectively. Seventy four underwent active surveillance. Both adjuvant therapies reduced the hazard of recurrence when compared to patients undergoing active surveillance: anti-PD1 HR: 0.32 (p < 0.01) and BRAFi/MEKi HR: 0.39 (p = 0.03). Anti-PD1-treated patients with a BRAF V600 mutation had a shorter RFS than patients with BRAF WT melanoma (p < 0.01); this was validated in external data where the presence of a BRAF V600 mutation was associated with an increased hazard recurrence (HR: 2.1, p = 0.025). CONCLUSION: Adjuvant systemic therapy improved RFS in our cohort. We found that BRAF V600 mutation was associated with a worse RFS for adjuvant anti-PD1 monotherapy. The effect of BRAF mutation on the response to anti-PD1 therefore may be considered when choosing between adjuvant anti-PD1 and BRAFi/MEKi for patients with BRAF V600 mutant melanoma.

Supplementary Figure 3 from Concordance between Tumor Tissue and Plasma DNA Genotyping in the NCI-MATCH Trial (EAY131)

2025-10-15

&lt;p&gt;Supplementary Figure 3. Genomic alterations detected in patients treated in subprotocol G enrolling patients with ROS1 translocations who received treatment with crizotinib. Patients are stratified according to the best overall response. Triangles are used to depict the presence of mutation in tissue (lower triangle) and/or plasma (upper triangle).&lt;/p&gt;

supplementary table TS1 from National Cancer Institute Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH)

2025-11-25

&lt;p&gt;supplementary table TS1&lt;/p&gt;

Supplementary Table 3 from Ipatasertib in Patients with Tumors with &lt;i&gt;AKT&lt;/i&gt; Mutations: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1K

2025-12-01

&lt;p&gt;Supplementary Table 3. Molecular characteristics and clinical outcomes with confirmed PR or PFS &gt;/6mo.&lt;/p&gt;

Supplementary Data 1 from Ipatasertib in Patients with Tumors with &lt;i&gt;AKT&lt;/i&gt; Mutations: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1K

2025-12-01

&lt;p&gt;Supplementary Data 1. Study Protocol.&lt;/p&gt;

Data from Ipatasertib in Patients with Tumors with &lt;i&gt;AKT&lt;/i&gt; Mutations: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1K

2025-12-01

&lt;div&gt;AbstractPurpose:&lt;p&gt;Activating mutations in &lt;i&gt;AKT&lt;/i&gt; genes are rare but play an important role in the commonly dysregulated PI3K/AKT/mTOR signaling pathway in multiple cancers. NCI-MATCH (EAY131) is a tumor-agnostic platform trial that enrolled patients to targeted therapies based on matching tumor genomic alterations. Subprotocol Z1K evaluated ipatasertib, a pan-AKT inhibitor, in patients with &lt;i&gt;AKT1&lt;/i&gt;&lt;sup&gt;E17K&lt;/sup&gt;-mutant metastatic tumors.&lt;/p&gt;Patients and Methods:&lt;p&gt;Patients received ipatasertib 400 mg orally once daily in a 28-day cycle until progression or unacceptable toxicity. Patients with well-controlled diabetes were eligible. Patients with known &lt;i&gt;KRAS&lt;/i&gt;, &lt;i&gt;NRAS&lt;/i&gt;, &lt;i&gt;HRAS&lt;/i&gt;, or &lt;i&gt;BRAF&lt;/i&gt; mutations were excluded. Prior PI3K and mTOR inhibitors were allowed. Prior AKT inhibitors were excluded. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival, 6-month progression-free survival, and toxicity.&lt;/p&gt;Results:&lt;p&gt;Thirty-five patients were enrolled, and 29 patients were included in the prespecified primary efficacy analysis. Multiple histologies were enrolled, with breast (&lt;i&gt;n&lt;/i&gt; = 18) and gynecologic (&lt;i&gt;n&lt;/i&gt; = 7) being the most common. The majority had &gt;3 lines of prior therapy (19/29; 65.5%). The ORR was 24.1% (7/29; 90% confidence interval, 11.9%–40.6%) with &lt;i&gt;P&lt;/i&gt; &lt; 0.001 against a null rate of 5%. All responses were partial responses. The median response duration was 10.1 months (90% confidence interval, 3.7–10.8). The most common toxicities of any grade included diarrhea (&lt;i&gt;n&lt;/i&gt; = 25), nausea (&lt;i&gt;n&lt;/i&gt; = 13), and hyperglycemia (&lt;i&gt;n&lt;/i&gt; = 9). Grade 3/4 toxicities observed were consistent with reported toxicities for AKT inhibition. Twelve grade 3 events occurred that were thought to be at least possibly related to treatment.&lt;/p&gt;Conclusions:&lt;p&gt;The study met its primary endpoint with an ORR of 24.1% (&lt;i&gt;P&lt;/i&gt; &lt; 0.001), with ipatasertib demonstrating clinically significant activity in heavily pretreated patients with various tumors harboring &lt;i&gt;AKT1&lt;/i&gt;&lt;sup&gt;E17K&lt;/sup&gt; mutations.&lt;/p&gt;&lt;p&gt;&lt;a href="https://aacrjournals.org/clincancerres/article-abstract/doi/10.1158/1078-0432.CCR-25-2640" target="_blank"&gt;&lt;i&gt;See related commentary by Dahmer Tiecher and Schram, p. 4863&lt;/i&gt;&lt;/a&gt;&lt;/p&gt;&lt;/div&gt;

Supplementary Figure 8 from Concordance between Tumor Tissue and Plasma DNA Genotyping in the NCI-MATCH Trial (EAY131)

2025-10-15

&lt;p&gt;Supplementary Figure 8. Genomic alterations detected in patients treated in subprotocol Z1A enrolling patients with NRAS mutations who received treatment with binimetinib. Patients are stratified according to the best overall response. Triangles are used to depict the presence of mutation in tissue (lower triangle) and/or plasma (upper triangle).&lt;/p&gt;

Supplementary Figure 2 from Ipatasertib in Patients with Tumors with &lt;i&gt;AKT&lt;/i&gt; Mutations: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1K

2025-12-01

&lt;p&gt;Supplementary Figure 2. Comutations in patients with AKT1 E17K mutations.&lt;/p&gt;