Purpose: No standard treatment exists for platinum-refractory, recurrent/metastatic nasopharyngeal cancer (NPC). This phase II study (NCT02605967) evaluated progression-free survival (PFS) of spartalizumab, an antiprogrammed cell death protein-1 (PD-1) monoclonal antibody, versus chemotherapy, in NPC.Patients and Methods: Patients with nonkeratinizing recurrent/metastatic NPC who progressed on/after platinum-based chemotherapy were enrolled. Spartalizumab was dosed 400 mg once every 4 weeks, and chemotherapy was received per investigator's choice.Results: Patients were randomized to receive either spartalizumab (82 patients) or chemotherapy (40 patients). The most common spartalizumab treatment-related adverse events were fatigue (10.3%) and pruritus (9.3%). Median PFS in the spartalizumab arm was 1.9 months versus 6.6 months in the chemotherapy arm (P = 0.915). The overall response rate in the spartalizumab arm was 17.1% versus 35.0% in the chemotherapy arm. Median duration of response was 10.2 versus 5.7 months in the spartalizumab versus chemotherapy arms, respectively. Median overall survival was 25.2 and 15.5 months in the spartalizumab and chemotherapy arms, respectively. Tumor RNA sequencing showed a correlation between response to spartalizumab and IFNγ, LAG-3, and TIM-3 gene expression.Conclusions: Spartalizumab demonstrated a safety profile consistent with other anti–PD-1 antibodies. The primary endpoint of median PFS was not met; however, median overall survival and median duration of response were longer with spartalizumab compared with chemotherapy.

Purpose: HER2/neu is overexpressed in up to 30% of gastroesophageal adenocarcinomas (GEA) and linked to poor prognosis. Recombinant mAbs to treat HER2/neu-overexpressing cancers are effective with limitations, including resistance and toxicity. Therefore, we developed a therapeutic B-cell epitope vaccine (IMU-131/HER-Vaxx) consisting of three fused B-cell epitopes from the HER2/neu extracellular domain coupled to CRM197 and adjuvanted with Montanide. This phase Ib study aimed to evaluate the optimal/safe dose leading to immunogenicity and clinical responses (https//clinicaltrials.gov/ct2/show/NCT02795988).Patients and Methods: A total of 14 patients with HER2/neu-overexpressing GEA were enrolled, and dose escalation (10, 30, 50 μg) was performed in three cohorts (C). Immunogenicity was evaluated by HER2-specific Abs and cellular responses, clinical responses by CT scans according to RECIST version 1.1.Results: IMU-131 was safe without vaccine-related significant local/systemic reactions or serious adverse events. A total of 11 of 14 patients were evaluable for changes in tumor size and vaccine-specific immune responses. One patient showed complete, 5 partial responses, and 4 stable diseases as their best response. HER2-specific IgG levels were dose dependent. In contrast to patients in C1 and C2, all patients in C3 mounted substantial HER2-specific Ab levels. In addition, cellular vaccine responses, such as Th1-biased cytokine ratios and reduced regulatory T cell numbers, were generated. Progression-free survival was prolonged in C3, correlating with the vaccine-specific humoral and cellular responses.Conclusions: IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose dependent and correlated with clinical responses. The highest dose (50 μg) was recommended for further evaluation in a phase II trial, with chemotherapy + IMU-131 or chemotherapy alone, which is currently ongoing.

No data regarding the efficacy of a third mRNA vaccine for solid cancer patients previously primed with the heterologous CoronoVac/ChAdOx1 vaccination implemented in Thailand during the shortage of vaccine supply are available. Forty-four cancer patients who previously received the heterologous CoronaVac-ChAdOx1 regimen were boosted with a third mRNA COVID vaccine, either BNT162b2 or mRNA-1273. Anti-RBD IgG was measured immediately before, two weeks after, and four weeks after the third dose. The antibody response was compared to 87 age- and gender-matched cancer patients who were primed with the homologous ChAdOx1/ChAdOx1 regimens. Post-third dose anti-RBD IgG levels significantly increased compared to pre-third dose levels. There was no statistical difference in post-third dose antibody titers or neutralization levels between these two primary series regimens. Treatment with chemotherapy was associated with a lower antibody response compared to endocrine therapy/biologics. Similar antibody levels were observed after a third booster with either BNT162b2 or mRNA-1273 following heterologous CoronaVac/ChAdOx1 vaccination. There was no statistical difference in the immune response following the third-dose vaccination between cancer patients and healthy individuals who received the same heterologous CoronaVac/ChAdOx1 vaccination. In conclusion, a similar degree of enhanced immunogenicity was observed after a third mRNA COVID-19 vaccination in solid cancer patients who previously received the heterologous CoronaVac/ChAdOx1 regimens.

Background: Amphiregulin (AREG) is one of the epidermal growth factor receptor (EGFR) ligands and plays the important roles in tumor progression and metastasis. Upregulation of AREG in colorectal cancer (CRC) tissues has been shown to correlate with depth of tumor invasion, nerve invasion and liver metastasis. We sought to investigate a correlation of serum AREG in CRC with clinicopathological parameters. Methods: Patients with CRC receiving treatment at King Chulalongkorn Memorial Hospital during August 2013 to March 2014 were enrolled. We collected baseline serum prior to start any therapy and stored till analysis. Serum AREG was measured by ELISA. The correlation between each clinicopathological characteristic and serum AREG was analysed. Results: There were 120 patients with CRC including 78 patients (65.0%) with stage I–III and 41 patients (34.2%) in stage IV or recurrent disease. In stage IV or recurrent group, the median level of serum AREG was 31.55 pg/mL, which was higher than those of stage I–III group, 15.48 pg/mL, P=0.001. The serum AREG higher than 25 pg/mL (high serum AREG) was significantly correlated with liver and peritoneal metastasis (P<0.001). Additionally, high serum AREG was significantly correlated with more poor differentiated/mucinous histological grade (P=0.014), distant metastasis (P=0.001), lymphovascular invasion (P=0.016) and perineural invasion (P<0.001). Conclusions: High serum AREG was associated with advanced diseases and poor pathologic factors in CRC. It is potentially a prognostic marker in CRC.

PURPOSE: Atezolizumab plus bevacizumab treatment is a first-line therapy for unresectable hepatocellular carcinoma (HCC) worldwide. The efficacy, safety, and patient-reported outcomes (PROs) of HCC in Thailand have not yet been reported. This study aimed to evaluate the efficacy, safety, and PROs of atezolizumab plus bevacizumab.MATERIALS AND METHODS: From September 2020 to August 2021, 30 patients with unresectable HCC who met the inclusion criteria of atezolizumab plus bevacizumab as first-line treatment were enrolled. Analysis was assessed for progression-free survival, overall survival, adverse events (AEs), and quality of life (QoL).RESULTS: The median progression-free survival and overall survival periods were 6.7 and 10.2 months, respectively. The disease control rate was 63.3%. The frequent AEs were proteinuria, hypertension, and hepatitis. Serious AEs included gastrointestinal bleeding, but none of the patients died from serious AEs. The discontinuation rate was 23.3%, and the median number of treatment cycles was 10.5 cycles. In total, 23.3% of the patients continued treatment after 1 year of therapy. The global health status/QoL and physical function scores showed less deterioration at baseline than at 3 and 6 months (median scores = 76.7, 71.6, and 64.1 in QoL and 84.7, 79.6, and 79.0 in physical function, respectively). The HCC18 symptom score index data showed a slow progression of symptom scores from baseline to 3 and 6 months (12.7, 19.6, and 22.3, respectively).CONCLUSION: This study demonstrates that atezolizumab plus bevacizumab is effective and has a safety profile comparable with that of previous studies as first-line therapy for unresectable HCC in a real-world setting and in Thai populations. Data on PROs also demonstrate benefits in terms of patients' QoL and symptoms.