Publications by authors named "Divya Sakamuri"
Article Synopsis
- This study focused on the effectiveness of perioperative immunotherapy in early-stage hepatocellular carcinoma (HCC) patients, specifically looking at tissue and imaging biomarkers during a phase II clinical trial.
- Nineteen patients receiving either neoadjuvant nivolumab combined with ipilimumab or nivolumab alone showed that major pathologic response (MPR) was linked to larger tumors initially, but a significant reduction in size post-treatment and increased immune activity markers like CD8 and granzyme B.
- The findings suggest that changes in tumor size and immune cell dynamics could serve as potential predictors for how well patients respond to neoadjuvant immunotherapy in treating resectable HCC.*
Article Synopsis
- Hepatocellular carcinoma (HCC) has high recurrence rates after surgery, and there are currently no approved standard therapies for pre- or post-surgery treatment, prompting the exploration of immunotherapy options.
- A phase 2 trial involved assigning patients with resectable HCC to receive either nivolumab alone or in combination with ipilimumab, assessing safety, tolerability, and secondary outcomes like overall response and progression-free survival.
- The trial enrolled 30 patients, finding that adverse events were more common in the combination treatment group (43%) compared to nivolumab alone (23%), with liver enzyme increases being the most reported side effect.
Background: BRAF inhibitors are effective in melanoma and other cancers with BRAF mutations; however, patients ultimately develop therapeutic resistance through the activation of alternative signaling pathways such as RAF/RAS or MET. The authors hypothesized that combining the BRAF inhibitor vemurafenib with either the multikinase inhibitor sorafenib or the MET inhibitor crizotinib could overcome therapeutic resistance.
Methods: Patients with advanced cancers and BRAF mutations were enrolled in a dose-escalation study (3 + 3 design) to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of vemurafenib with sorafenib (VS) or vemurafenib with crizotinib (VC).
Purpose: Intratumorally injected -NT (nontoxic; lacking the alpha toxin), an attenuated strain of , replicates within hypoxic tumor regions resulting in tumor-confined cell lysis and inflammatory response in animals, which warrants clinical investigation.
Patients And Methods: This first-in-human study (NCT01924689) enrolled patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection of -NT across 6 dose cohorts (1 × 10 to 3 × 10 spores, 3+3 dose-escalation design) to determine dose-limiting toxicities (DLT), and the maximum tolerated dose.
Results: Among 24 patients, a single intratumoral injection of -NT led to bacterial spores germination and the resultant lysis of injected tumor masses in 10 patients (42%) across all doses.
Preclinical data suggest that combining a checkpoint inhibition with immunomodulatory derivative can increase anticancer response. We designed a dose-escalation study using a 3 + 3 design to determine the safety, maximum tolerated dose (MTD) or recommended phase II dose (R2PD) and dose-limiting toxicities (DLT) of the anti-CTLA-4 antibody ipilimumab (1.5-3 mg/kg intravenously every 28 days × 4) and lenalidomide (10-25 mg orally daily for 21 of 28 days until disease progression or unacceptable toxicity) in advanced cancers.
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