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Background: The HER2-targeted drugs selection after trastuzumab failure has become a challenging issue for HER2-positive metastatic breast cancer (MBC) patients. Inetetamab is a neotype of HER2-targeted monoclonal antibody with an engineered Fc segment that optimizes the antibody-dependent cell-mediated cytotoxicity (ADCC) effect, which was important for disease control. Moreover, HER2-targeted tyrosine kinase inhibitors, as pyrotinib, were found to further improve the ADCC effect of monoclonal antibodies in pre-clinical researches, indicating that the combination of pyrotinib and inetetamab could achieve complementarity and synergy effects in terms of short-term tumor killing effect and long-term immunotherapy benefits. Therefore, the combined treatment pattern of the two drugs has potential clinical benefits. Methods: This is a prospective, multi-center, single-arm clinical study designed to evaluate the efficacy and safety of pretreated patients with HER2-positive MBC. We recruited patients with pathologically confirmed HER2-positive MBC who had received 1-3 prior regimens for metastatic disease, which must include trastuzumab. The enrolled patients received 6 cycles of Inetetamab combined with pyrotinib and chemotherapy, subsequent maintenance therapy should be considered according to tolerability. The chemotherapy drugs were decided by physicians’ choice, and could be microtubules, anthracyclines, or antimetabolites. The primary endpoint was objective response rate (ORR) after 6 cycles of treatment, secondary endpoints included progression-free survival (PFS), overall survival (OS), and clinical benefit rate (CBR) and adverse events (AEs). Results: 57 patients were enrolled from October 2020 to July 2022. And 45 patients were available for response evaluation. The ORR and DCR were 53.5 % (24/45) and 86.7 % (39/45), respectively after 6 cycles treatment. The median PFS was 7.3 months. The incidence of grade Ⅲ-Ⅳ AEs was 15.8 %. The most common treatment-related AEs were diarrhea, anemia, neutropenia, leukopenia, hand and foot syndrome. No patient’ s left ventricle ejection fraction (LVEF) decreased to < 50% or decreased by >15%. And no significant decline in quality of life score was reported. Conclusion: Inetetamab combined with pyrotinib and chemotherapy showed a promising efficacy and a good tolerance in patients with HER2-positive metastatic breast cancer, confirming the synergistic effect between the ADCC optimized monoclonal antibodies and TKIs, which brings more treatment options for HER2-positive metastatic breast cancer. Citation Format: Jianli Zhao, Yangyang Cai, Linxiaoxiao Ding, Yaping Yang, Guorong Zou, Herui Yao, Ying Wang. Inetetamab combined with pyrotinib and Chemotherapy in Pretreated Patients with HER2-positive metastatic breast cancer, a single arm, multicenter phase II clinical trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-25-02.

PURPOSE Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer. METHODS This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety. RESULTS Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%). CONCLUSION Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

This paper presents a two-stage ejector-based multi-evaporator refrigeration system using R134a as the refrigerant and the effects of variable operating conditions such as back pressure and evaporating temperature and cooling loads on each stage are investigated by using CFD simulations. The simulation results indicate that: (1) three operational modes: critical mode, subcritical mode and back flow mode are available for each stage when two stages combine with each other, but the range of pressure lifting ratio generating subcritical and back flow modes is not the same with each other; (2) the entrainment ratio of the first-stage is mainly influenced by the variation of the evaporating temperature of refrigerating and freezing chambers, while the entrainment ratio of the second-stage of is more influenced by the change of the evaporating temperature of the air-conditioning chamber; (3) the effect of the mass flow rate of the first-stage primary flow on the entrainment ratio of the first-stage is more significant, while the effect of the mass flow rate of the second-stage primary flow on the entrainment ratio of the second-stage is more evident.

Background NPC is rare but has a distinct geographic distribution, with a predominance in Southeast Asia. Favorable results with PD-1 inhibitors in NPC provide a strong rationale to investigate penpulimab in this disease. Penpulimab was engineered to eliminate FcγR binding and ADCC/ADCP completely,where ADCC/ADCP effects can induce T-cell apoptosis and clearance and then compromise anti-tumor activity. Penpulimab demonstrated a slower PD-1 antigen binding off-rate than marketed PD-1 antibodies, which result in better cellular activity and higher receptor occupancy. Penpulimab also showed numerous contacts with N58 glycosylation on the BC loop of PD-1 which could be an advantage to facilitate interaction of PD-1 antibody and may contribute to slower binding off-rate. These structural differentiations offer more robust biological effect and enhance anti-tumor activity of penpulimab. Methods AK105-202 (NCT03866967) is a multicenter, single-arm, open-label study of penpulimab in metastatic NPC patients (pts) with disease progression after ≥2 prior lines of therapy including platinum-containing chemotherapy. All patients received penpulimab 200 mg q2w until progression or unacceptable toxicity. The primary endpoint was ORR based on RECIST v1.1 as assessed by an independent review committee (IRC). Key secondary endpoints included DCR, PFS, duration of response (DoR). Archived tissues were retrieved for the analysis of PD-L1 (Shuwen SAB-028). PD-L1 expression of tumor proportion score (TPS)≥50% was regarded as positive. Plasma Epstein-Barr virus DNA were obtained for biomarker correlative analysis. Results As of 18 September 2020, the median follow-up was 7.9 months (range 0.9 to 16.9). The anti-tumor activity of penpulimab in the 111 pts with disease progression after ≥2 prior lines of therapy evaluable for efficacy (defined as pts who had an opportunity to be followed for at least 16 weeks and had measurable disease at baseline per RECIST v1.1) is shown in the table 1. Treatment-related adverse events (TRAEs, including unlikely related) occurred in 79.2% of pts (≥G3 in 14.6% [19/130], treatment discontinuation in 3.1% [4/130]). Treatment-related SAEs occurred in 10.0% [13/130]. Most frequent TRAEs (≥10%) were fever (24.5%), hypothyroidism (24.6%), anemia (23.1%), ALT increased (17.0%) and WBC decreased (10.8%). Grade ≥3 TRAEs (≥2%) were hepatic function abnormal (2.3%) and anemia (2.3%). Conclusions Penpulimab demonstrated encouraging anti-tumor activity and favorable safety profile in pts with disease progression after ≥2 prior lines of therapy. A higher proportion of objective responses was observed in NPC pts with PD-L1–positive tumors receiving penpulimab than those with PD-L1–negative tumors.

Objectives: The aim of this study is to investigate the predictive value of smoking history on treatment outcomes of pemetrexed continuation maintenance therapy in advanced non-squamous NSCLC patients without EGFR mutations and ALK rearrangements. Methods: 71 consecutive EGFR and ALK negative advanced non-squamous NSCLC patients who had received pemetrexed continuation maintenance therapy at least two cycles were retrospectively analyzed in our single center. The enrolled patients were categorized into two groups as never-/former light smokers and current smokers according to their smoking history. Results: In the 71 non-squamous NSCLC patients, 30 (42.3%) were never-/former light smokers and 41 (57.7%) were current smokers. The objective response rate (ORR) of never-/former light smokers was significantly higher than that of current smokers (26.7% vs. 7.3%, p = 0.026). Never-/former light smokers showed significantly longer progression free survival (PFS) (6.6 [95% CI 5.3-7.9] months vs. 5.1 [95% CI 3.5-6.7] months; HR: 0.557, 95% CI 0.339-0.915, p = 0.021) and overall survival (OS) (17.3 [95% CI 14.4-20.2] months vs. 15.7 [95% CI 12.0-19.4] months; HR: 0.578, 95% CI 0.338-0.986, p = 0.044) than current smokers. Multivariate analysis identified smoking history was an independent predictive factor for PFS and OS. Conclusions: Current smoking is an independent negative predictive factor of outcomes for pemetrexed continuation maintenance therapy in advanced non-squamous NSCLC patients without EGFR mutations and ALK rearrangements.

TPS12133 Background: Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of cancer treatments, and dexamethasone offers an advantage over placebo for protection against chemotherapy-induced emesis in both acute and delayed phases. However, its side effects are diverse including moderate to severe insomnia, hyperglycemia, dyspepsia and so on, which are gathering increasing concerns. What’s more, dexamethasone is not applicable to all cancer patients. The incidence of diabetes mellitus varies in different cancer which can reach up to 55.3%, and dexamethasone might not be a proper anti-emesis choice for them. Besides, dexamethasone delivery is always on debating when patients are receiving immunotherapy. However, all anti-emesis regimen recommended in guidelines are dexamethasone based. Alternative anti-emesis regimen are required. Studies have shown that olanzapine plays an important role in treating delayed, refractory, breakthrough nausea and vomiting. Thus, we initiated this prospective, multi-center, phase III study to validate the dexamethasone-free protocol: the non-inferiority role of applying olanzapine to prevent CINV instead of dexamethasone. Methods: This clinical trial started on February 3, 2020 is being conducted in 23 centres. All patients eligible are chemotherapy naïve and plan to receive cisplatin-containing regimen. Based on a 70% complete remission rate of previous study, to demonstrate a non-inferiority margin of 10%, 548 patients are required for two arms with the consideration of 5% of drop out and lost to follow-up (80% power,α = 0.05). Study design: Enrolled patients are randomized 1:1 into 2 arms to receive olanzapine or dexamethasone combined with 5-HT3 receptor antagonist (palonosetron, granisetron or ondansetron) and NK-1 receptor antagonist (aprepitant or fosaprepitant) from the first day of chemotherapy. Olanzapine (5mg) is delivered orally per night from day 1 to day 4. Dexamethasone (12 mg) is given orally or intravenously within 30 minutes before cisplatin administrated on day 1; on day 2-4, the orally or intravenously given dose of dexamethasone is 8 mg. The primary endpoint is complete remission rate of vomiting during the whole observation period (0-120 hours from the starting of first course chemotherapy delivery). The secondary endpoints are complete remission rate of vomiting during 25-120 hours from the starting of first course chemotherapy delivery and no nausea rate during the whole observation period. Besides, side effects will be recorded according protocol. Clinical trial information: NCT04437017.

In this study, we proposed an automated method based on convolutional neural network (CNN) for nasopharyngeal carcinoma (NPC) segmentation on dual-sequence magnetic resonance imaging (MRI). T1-weighted (T1W) and T2-weighted (T2W) MRI images were collected from 44 NPC patients. We developed a dense connectivity embedding U-net (DEU) and trained the network based on the two-dimensional dual-sequence MRI images in the training dataset and applied post-processing to remove the false positive results. In order to justify the effectiveness of dual-sequence MRI images, we performed an experiment with different inputs in eight randomly selected patients. We evaluated DEU's performance by using a 10-fold cross-validation strategy and compared the results with the previous studies. The Dice similarity coefficient (DSC) of the method using only T1W, only T2W and dual-sequence of 10-fold cross-validation as different inputs were 0.620 ± 0.0642, 0.642 ± 0.118 and 0.721 ± 0.036, respectively. The median DSC in 10-fold cross-validation experiment with DEU was 0.735. The average DSC of seven external subjects was 0.87. To summarize, we successfully proposed and verified a fully automatic NPC segmentation method based on DEU and dual-sequence MRI images with accurate and stable performance. If further verified, our proposed method would be of use in clinical practice of NPC.

6021 Background: Camrelizumab is a fully humanized, monoclonal antibody against PD-1. We aimed to assess the efficacy and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor targeting VEGFR2, in patients with advanced cervical cancer. Methods: In this open-label, single-arm, phase 2 study done at four centres in China, eligible patients were aged 18–70 years, had an ECOG performance status of 0 or 1, progressed after at least one line of systemic chemotherapy for metastatic, recurrent or persistent cervical cancer, and had measurable disease. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once daily. Treatment continued until disease progression, unacceptable toxicity, and withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by RECIST version 1.1. An optimal Simon two-stage design was employed to test the null hypothesis of a 17% ORR versus 35% alternative (1-sided alpha 0.10, 80% power), if > 3 responses out of the first 16 patients were observed, then the study would continue to enroll a total of 44 patients. Results: Between Jan 21st, 2019, and Aug 1st, 2019, 45 patients were enrolled and received study treatment (safety population). The median age was 51 (range, 33–67) years. Median previous treatment lines were 2 (range, 1–4). As of Jan 22, 2020, median follow-up was 9.2 months (range, 2.4–12.2). 25 (59.5%; 95%: CI 44.7–74.4) of 42 patients who had at least one post-baseline tumor assessment (efficacy evaluable population) achieved an objective response, including two (4.8%) complete response, and 23 (54.8%) partial response. Median duration of response was not reached. The disease control rate was 88.1% (37/42). Median progression-free survival (PFS) was 7.6 months (95% CI: 5.8–not reached). 31 (68.9%) patients had grade ≥ 3 treatment-related adverse events (TRAEs). Grade ≥ 3 TRAEs occurring in ≥ 5% of patients were hypertension (24.4%), anemia (20.0%), fatigue (15.6%), γ-glutamyltransferase increased (13.3%), neutropenia (6.7%), and thrombocytopenia (6.7%). In post-hoc analyses, objective response was noted in 20 (69%) of 29 patients with PD-L1-positive tumors, and in 5 (50.0%) of 10 patients with PD-L1-negative tumors (Chi-square test, P = 0.281). PFS was longer in patients with PD-L1-positive tumors than patients with PD-L1-negative tumors (median PFS: 9.6 versus 5.3 months; log-rank test, P = 0.017). Conclusions: Camrelizumab plus apatinib showed promising antitumor activity and tolerable toxicities in patients with advanced cervical cancer. Clinical trial information: NCT03816553.

In this paper, a novel ejector-based multi-evaporator refrigeration system using R134a is proposed to meet different working modes of refrigerated trucks running in tropical regions. The Computational Fluid Dynamics (CFD) simulation is implemented to research the performance of ejectors utilized in both air conditioning - refrigerating mode and air conditioning - freezing mode. Consequently, crucial ejector geometrical parameters such as area ratio (AR), nozzle exit position (NXP), lengths of primary nozzle and diffuser are optimized for each mode. Moreover, a novel approach by taking the deviation of the entrainment ratio or secondary mass flow rate over the deviation of the geometrical parameter into account to evaluate the ejector performance sensitivity to each geometrical parameter is first time presented to the best of the authors’ knowledge. The results show that: 1) Area ratio, NXP, lengths of primary nozzle and diffuser of the ejector in the air conditioning - freezing mode are almost twice as those in the air conditioning - refrigerating mode; 2) The performance of both ejectors is primarily influenced by area ratio and NXP; 3) The proposed sensitivity indicator can better evaluate the sensitivity of the ejector performance to geometrical parameters.

Objective To analyze the clinicopathologic characteristics and prognosis of patients with squamous cell carcinoma localized to different supraglottic subregions. Methods Clinicopathologic data were reviewed retrospectively for 111 patients with supraglottic squamous cell carcinoma who were diagnosed between January 1, 1995 and December 31, 2005 and were initially treated with surgery. DNA from human papillomavirus (HPV) 16 and (or /and) HPV 18 were detected in all the 111 supraglottic carcinoma specimens using in situ hybridization. Survival analysis was performed by Kaplan-Meier analysis, factors were compared using log-rank test, and prognostic factors were determined using Cox proportional hazards model. The relationship between subregions and clinicopathologic factors was analyzed using Chi-square tests. Results HPV prevalence differed between patients with aryepiglottic fold carcinoma and ventricle carcinoma (P < .05). The local-regional control rates, overall survival rates or cancer specific survival rates were significantly different between different subregions. Univariate analysis indicated that pTNM classification, pN spread, and subregion were associated with prognosis (P < .05). Multivariate analysis indicated that pTNM classification and subregion were associated with supraglottic carcinoma prognosis. The survival rate was better for patients with carcinoma of the epiglottis or ventricular bands compared to those with carcinoma in the aryepiglottic fold or ventricle (P = .012). Conclusions Subregion may be a new prognostic factor for supraglottic squamous cell carcinoma. Different supraglottic carcinoma subregions have distinct clinical features such as HPV expression, lymph node metastasis rate, local-regional control and prognosis. Therefore, it is necessary to subdivide supraglottic squamous cell carcinomas into several subregion groups to individualize therapy.

To observe the changes in serum transforming growth factor-β1 (TGF-β1) in patients with early-stage nasopharyngeal carcinoma (NPC) after radiotherapy and explore the correlation of serum TGF-β1 with radiation injury and disease-free survival.The average serum TGF-β1 level (50.2∓3.2 ng/ml) determined from 32 healthy volunteers was used as the standard value for NPC patients in this trial. Fifty-seven patients with early-stage (T1-2N0-1M0) NPC without prior treatment were divided into two groups with serum TGF-β1 level before treatment lower than or equal to the standard value (group A, 29 cases) and a level beyond the standard value (group B, 28 cases). Serum TGF-β1 level was determined in all the patients before, during and after the radiotherapy to evaluate the radiation injury and therapeutic effect.The serum TGF-β1 level before radiotherapy was significantly lower in group A than in group B (35.4∓1.4 vs 58.8∓1.0 ng/ml, P0.05). After radiotherapy, acute radiation mucositis and skin reaction was significantly severer in group B (P0.05). The serum TGF-β1 level before radiotherapy was significantly higher in patients with grade 3 acute radiation mucositis and skin reaction than in those with injuries below grade 3 (54.0∓2.2 vs 42.0∓2.3 ng/ml and 54.3∓2.4 vs 43.4∓2.2 ng/ml, P0.05). The two groups showed no significant differences in the locoregional failure rate (3.4% vs 7.1%), distant metastasis rate (3.4% vs 10.8%) or disease-free survival (P0.05).Radiotherapy can significantly decrease serum TGF-β1 level in early NPC patients. Serum TGF-β1 level before radiotherapy can help predict the degree of acute radiation mucositis and skin reaction, but shows no correlation with disease-free survival of early-stage NPC patients.