tbuckley/cabot-search huggingface dataset:
Utidelone for heavily pretreated metastatic castration-resistant prostate cancer after failing docetaxel treatment: An open-label, single-arm, phase II trial.
Authors: Meiting Chen, Xin An, Cong Xue, Haifeng Li, Wei Yang, Riqing Huang, Jing Peng, Li Tang, Jun Wang, Yonghong Li, Yanxia Shi
Journal: Journal of Clinical Oncology (2024)

e17036 Background: The appropriate chemotherapy for metastatic castration-resistant prostate cancer (mCRPC) that progressed after docetaxel treatment remains unmet medical needs. Utidelone (UTD1) is a genetically engineered epothilone analog with antitumor activity in taxane-resistant cancers. UTD1 was approved for advanced breast cancer in 2021. This study was designed to evaluate the safety and efficacy of UTD1 in mCRPC. Methods: In this perspective, phase II clinical trial, men with progressive mCRPC after docetaxel and abiraterone, and/or enzalutamide, and/or apalutamide received UTD1 monotherapy treatment at a total dose of 150 mg/m 2 for five days intravenous, every three weeks until disease progression, or intolerable toxicity, or death. We reported the preliminary results for potential benefits in this new treatment. The primary endpoint was prostate specific antigen (PSA) response rate, defined as a 50% or greater reduction in serum PSA. The secondary endpoint included investigators-assessed objective response rate (ORR) and disease control rate (DCR) according to RECIST v1.1, radiographic progression-free survival (rPFS) according to PCWG3 criteria, overall survival (OS), and safety. The trial was registered at Chinese Clinical Trial Registry (No. ChiCTR2200061635). Results: By January 31 st , 2024, twenty-five mCRPC patients with a median age of 67 years were enrolled in this study at Sun Yat-sen University Cancer Center since March 23 rd , 2022. Patients received an average of 4.2 lines of prior anticancer treatments: 100% of them received docetaxel, 96.0% of them received abiraterone, and 80.0% progressed after enzalutamide, and/or apalutamide. 28.0% of patients had visceral metastases, and 88.0% patients had bone metastases. At of the cut-off date, the PSA response rate was 16.0%. The median rPFS and OS were 4.9 months and 7.1 months, respectively. One patient had a durable response for 19.2 months and had been remaining on study treatment to date. One PR and four SD were observed in ten patients with measurable lesions, resulting in an overall ORR and DCR of 10.0% and 50.0%, respectively. The most common treatment-related adverse events (TRAEs) including peripheral sensory neuropathy (76.0%), dyspepsia (72.0%), anemia (64.0%), constipation (60.0%), fatigue (64.0%), nausea (36.0%), leukocytopenia (32.0%), arthralgia (32.0%), dizziness (32.0%), vomiting (20.0%), and diarrhea (20.0%) were manageable. The 3/4 grade TRAEs included anemia (16.0%), and diarrhea (4%). No treatment-related death occurred. Conclusions: UTD1 has demonstrated promising efficacy and favorable tolerance in heavily pretreated mCRPC patients after progression on docetaxel in the preliminary analyses. Additional randomized trials are warranted for this new regimen. Clinical trial information: ChiCTR2200061635.
Magnesium microspheres to enhance lipiodol-mediated transarterial chemo-embolization (TACE) of hepatocellular carcinoma: From bench to a pilot clinical study.
Authors: Liyun Zheng, Jiansong Ji
Journal: Journal of Clinical Oncology (2024)

e16204 Background: Transarterial chemoembolization (TACE) has been extensively used in clinic to treat unresectable hepatocellular carcinoma (HCC). However, arterial embolization would worsen the hostile physicochemical features in the tumor microenvironment (TME) by further reducing its pH and increasing hypoxia, leading to immunosuppressive TME and drug resistance. Methods: Magnesium microspheres (Mg MSs), acting as H2 donors and pH modulators, were prepared via gas atomization pulverization. Characterization included inverted optical microscopy, SEM, and XRD analysis. Their H2 generation and acid neutralization capabilities were confirmed. The Lip-Mg dispersion (Mg MSs dispersed in lipiodol) was tested for therapeutic efficacy in H22 murine liver tumor-bearing mice, 4T1, and CT26 subcutaneous tumor models, as well as in vivo interventional TAE therapy for rabbit orthotopic liver tumors. The modulated capacities of Lip-Mg in H2 gas generation, acid neutralization, and promotion of antitumor immune response were investigated in vivo. Finally, a single-center, single-arm, open-label trial (ChiCTR2200064999) evaluated the safety and efficacy of TACE treatment with Lip-Mg (M-TACE) in Chinese HCC patients. Results: Inverted optical microscopy and SEM images confirmed uniform, smooth Mg microspheres (~60 μm) with a grayish-white color. In acidic buffer (pH 6.4), Mg microspheres rapidly increased pH, as measured by pH meter or fluorescent probe. Lip-Mg treatment significantly inhibited tumor growth compared to controls, prolonging mouse survival by ~2-fold, validated in 4T1 and CT26 models. Ultrasonic and multispectral fluorescence imaging demonstrated Lip-Mg's ability to release H2 and neutralize pH in vivo, reversing the immunosuppressive tumor microenvironment. Clinical study showed manageable treatment-related adverse events, with no unexpected toxicities and negligible impact on serum magnesium levels, confirming the safety of Mg microspheres for M-TACE. According to mRECIST, M-TACE exhibited high CR (61.5%), PR (38.5%), and ORR (100%) rates, with an overall response rate and CR rate of 90% and 60%, respectively. Conclusions: Metallic Mg microspheres (~60 μm) were developed to enhance lipiodol-mediated TAE/TACE for HCC. When combined with lipiodol and injected, they neutralized the acidic TME, triggered hydrogen therapy, and reversed immunosuppression, effectively inhibiting tumor growth. Lip-Mg showed superior outcomes to lipiodol alone for TAE therapy, with M-TACE treatment exhibiting higher ORR and CR rates than cTACE. Post-M-TACE, adverse events were managed well without treatment discontinuations. Our study introduces Mg microspheres as a promising embolic device for M-TACE therapy, potentially improving TACE benefits. Clinical trial information: ChiCTR2100050327.
A phase II study of anlotinib plus albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or peritoneal carcinomar (A-Plus trial): Updated efficacy and safety.
Authors: Yanfang Li, Yun Zhou, Jian Zhou
Journal: Journal of Clinical Oncology (2024)

5557 Background: Initial results of the open-label, single-arm phase II clinical trial, we had demonstrated anlotinib plus albumin-bound paclitaxel treatment activity and favorable tolerance in patients with recurrent, platinum-resistant primary epithelial ovarian or peritoneal carcinoma (SGO 2023. Oral featured poster 549). Here we update the latest efficacy and safety data in enrolled patients. Methods: In this study, 44 patients diagnosed with platinum-resistant or platinum-refractory ovarian cancer were planned to be enrolled. Patients received ab-paclitaxel 260 mg/m2 given by intravenous infusion over 30 min every 3 weeks and anlotinib (10mg, po, qd, for 14 days, every 3 weeks) until disease progression or intolerable toxicity. For efficacy evaluation, the following were required: measurable disease defined by RECIST 1.1, or if there were no measurable lesions but an elevated CA125 with significant symptoms such as abdominal pain, bloating, or pleural effusion/ascites (Rustin criteria). The primary end point were investigator-confirmed objective response rate (ORR). Results: From January 2021 to March 2023, 44 patients were enrolled with a median age of 49 years(range, 40-66). 29 patients had measurable lesions and 15 patients had no measurable lesions but an elevated CA125 evaluated according to Rustin criteria. As of efficacy evaluation, 43 out of 44 patients can be analyzed and one without measurable lesions can not be included due to the absence of a post-treatment data. Among the 29 patients with measurable lesions, 16 (55.2%; 95% CI 0.359-0.730) achieved objective responses, including CR in two patients, PR in fourteen, stable disease in thirteen, and PD in zero. In the group of 14 patients without measurable lesions, 9 (60%; 95% CI 0.328-0.825) achieved responses, including CA 125 responses in nine patients, CA 125 no response in four, and CA125 disease progression in one. Overall responses were observed in 25 out of 44 patients (56.8%; 95% CI 0.411-0.713) in the intention-to-treat population, and in the per-protocol population, the response was seen in 25 out of 43 patients (58.1%; 95% CI 0.422-0.726). The grade 3/4 AEs encompassed leukopenia (31 patients, 70.5%), gum-pain (10 patients, 22.7%), hypertension (10 patients, 22.7%), Hand-foot syndrome (4 patients, 9.1%). Conclusions: Updated results reconfirm a favorable antitumor activity and manageable safety from anlotinib plus albumin-bound paclitaxel in the treatment of recurrent ovarian or peritoneal carcinoma. Further survival results are expected. Clinical trial information: ChiCTR2100054329.
Neoadjuvant cadonilimab (PD-1/CTLA-4 bispecific antibody) plus FLOT chemotherapy in locally advanced gastric/gastroesophageal junction cancer (GC/GEJC): A prospective, multi-center, phase II study.
Authors: Zuoyi Jiao, Huinian Zhou, Zyuaun Yu, Bo Long, Zeping Huang, Da Zhao, Dengwen Wei, Xiaonin Zhao, Zebin Jiang, Xiaojun Yang
Journal: Journal of Clinical Oncology (2024)

e16108 Background: FLOT remains the preferred neoadjuvant treatment (NAT) for locally advanced GC/GEJC, with evidence suggesting enhanced efficacy when plus PD-1 inhibitors. Cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, also exhibited survival benefits when combined with chemotherapy as first-line treatment for GC/GEJC. This study aimed to assess the efficacy and safety of Cadonilimab and FLOT as NAT in locally advanced GC/GEJC. Methods: Pathologically confirmed treatment-naïve patients (pts), aged 18-75, with radiologically evaluable primary GC/GEJC at stage cT3/4, ECOG PS 0-1, were enrolled. The study used simon-2 stage design with a total sample size of 38 pts and would be considered effective if more than 4 pts achieved pCR. Pts received surgery after completing NAT with Cadonilimab (10mg/kg, iv, Q3W) and FLOT (50mg/m² docetaxel, 85mg/m² oxaliplatin, 2600mg/m² 5-FU, and 200mg/m² leucovorin, iv). The primary endpoints were pCR and MPR rate. Secondary endpoints included ORR, DCR, R0 resection rate and safety (CTCAE 5.0). Results: In this phase II trial, initially enrolled 29 pts in stage I, with an additional 9 pts in stage II. Of the 34-evaluable pts, 30 pts underwent surgery. The median age was 57 years (range, 38-74), with 88.2% male and 64.7% diagnosed as stage cT4. According to RECIST1.1 criteria, 5 pts (14.7%) achieved CR, and 21pts (61.8%) achieved PR, with an ORR of 76.5% and DCR of 100.0%. According to Becker criteria for Tumor Regression Grade: 6 pts (20.0%) achieved TRG1a, 9 pts (30.0%) reached TRG1b, with a pCR rate of 20.0% and MPR rate of 50.0%. Pts with diffused and poorly differentiated tumors had higher rates of pCR and MPR (36.4%, 81.8%) than the overall population. A notable tumor downstaging was observed: 86.7% in T stage, 70.0% in N stage, and 70.0 in overall TNM stage. During the NAT phase, all 34 pts experienced TRAEs. Mild to moderate TRAEs (grade 1-2) were observed in 73.5% (25 patients), while 26.5% (9 patients) experienced grade 3 TRAEs. There were no reports of grade 4-5 or severe TRAEs. The most common TRAEs were nausea (100.0%), alopecia (97.1%), vomiting (85.3%), fatigue (85.3%), electrolyte disturbance (79.4%) and rash (73.5%). In post-surgery, all 30 pts achieved R0 resection. Surgical complications were relatively minor, predominantly fever (46.7%), ascites (30.0%) and pneumonia (23.3%). The survival benefit will be reported after the follow-up completed. Conclusions: Neoadjuvant Cadonilimab plus FLOT chemotherapy exhibit encouraging anti-tumor effectiveness and manageable toxicities, particularly in pts with diffused Lauren`s classification and poorly differentiation. This immunochemotherapy regimen might provide a promising alternative NAT option for locally advanced GC/GEJC. Clinical trial information: ChiCTR2200066893.
Tislelizumab in combination with GEMOX and lenvatinib for conversion therapy of unresectable extrahepatic biliary tract carcinoma (eBTC): A prospective, single-arm, phase 2 study.
Authors: Qu Liu, Zhengyu Chang, Guodong Zhao, Yuanxing Gao, Xianglong Tan, Xuan Zhang, Hailong Jin, Rong Liu
Journal: Journal of Clinical Oncology (2024)

e16163 Background: Resection is the only possibility for cure but only less than 1/3 patients with BTC are diagnosed at resectable stages. PD-1 monoclonal antibody plus GEMOX and Lenvatinib regimens have shown promising efficacy for intrahepatic cholangiocarcinoma. However, owing to the extrahepatic and intrahepatic BTC are highly heterogeneous, the efficacy of combination regimen on eBTC is not clear. In this study, we explored the efficacy and safety of Tislelizumab plus GEMOX and Lenvatinib for conversion therapy of unresectable eBTC. Methods: In this prospective, single-arm phase 2 study, major eligible criteria were unresectable locally advanced or metastatic extrahepatic BTC, no previous systemic treatment, ECOG PS 0 or 1. Patients received tislelizumab (200 mg, iv, d1, every 3 weeks) in combination with GEMOX (gemcitabine: 1000 mg/m 2 , iv, d1,d8, every 3 weeks; oxaliplatin: 85 mg/m 2 , iv, d1, every 3 weeks) and Lenvatinib (bodyweight ≥ 60 kg: 12 mg/day; &lt; 60 kg: 8 mg/day, po) until disease progression, intolerable toxicity or surgery. Surgery was performed after treatment response was assessed to meet the criteria of resection. Primary endpoint was the rate of radical resection. Second endpoints included ORR, DCR per RECIST 1.1, and safety, major pathologic response (MPR), PFS, OS. Results: Between Mar 1 st 2022 and Feb 1 st 2024, 35 patients were enrolled with a median age of 57.5 years (range 52-65); 20 males (57.1%), 15 females (42.9%); ECOG PS 0 (n = 13, 37.1%) or 1 (n = 17, 62.9%); 7 distal cholangiocarcinoma (20.0%), 16 hilar cholangiocarcinoma (45.7%), 12 gallbladder carcinoma (34.3%). 30 patients were evaluated for tumor response. The best overall responses were 2 complete response (6.7%), 16 partial response (53.3%), 9 stable disease (30.0%) and 3 progressive disease (10.0%). The ORR was 60.0% and DCR was 90.0%. 7 patients (20.0%) received radical resection and the complete pathological response (pCR) rate was 42.9% (n = 3). Any-grade adverse events (AEs) occurred in 91.4% (n = 32) patients. Grade 3-4 AEs occurred in 20.0% (n = 7) patients. The most frequent grade 3-4 AEs (incidence &gt; 5%) were thrombocytopenia (8.6%), elevated AST/ALT (8.6%), neutropenia (5.7%) and leukopenia (5.7%). No grade 5 AEs. Conclusions: Tislelizumab plus GEMOX and Lenvatinib showed promising efficacy with manageable safety profile for conversion therapy of unresectable extrahepatic BTC. More patients were recruiting to further prove these results. Clinical trial information: ChiCTR2200056808.
The activity and safety of icaritin for patients with unresectable HCC: A real world, retrospective study.
Authors: Guoliang Shao, Wentao Jiang, Xin Zheng, Huiling Xiang, Song Wang, Xu Zhou, Nan Lin, Zheng-Ping Yu, Ke Dong, Mingrong Cao, Qinfen Xie, Hui Zeng, Zhewei Zhang, Jun Luo
Journal: Journal of Clinical Oncology (2024)

e16181 Background: Primary liver cancer is a major health burden globally, ranking sixth in incidence and third in mortality among all cancers[1]. Over the past 5 years, immune checkpoint inhibitors (ICIs) and multi-targeted tyrosine-kinase inhibitors have emerged as new treatment options for advanced hepatocellular carcinoma[2–4]. Nevertheless, only a small subset of patients with hepatocellular carcinoma derive a response to ICI monotherapy. Icaritin, a target tumor micro-environment(TME) modulating compound, which interacts with MyD88/IkB kinase-a (IKK)[5], inhibiting the TNF-a-induced IKK and nuclear factor-κB (NF-kB) signaling pathways and blocking PD-L1 expression in HBV-related HCC[6-9] and has been approved in China for the treatment of first-line advanced HCC. Icaritin phase III study previously reported at 2021 ASCO, we therefore investigated the efficacy of icaritin in patients with unresectable stage IIA-IIIB (CNLC stage) HCC in a real-world setting. Methods: This multi-center, retrospective study, conducted between May 2022 and Nov 2023. We retrospectively collected medical records of patients (pts) with unresectable IIA-IIIB (CNLC stage) HCC who received icaritin monotherapy (mono-group) or icaritin combined with PD-1/L1 and/or anti-VEGF therapy (combination group) as first line therapy. The primary endpoints were progression free survival (PFS); Secondary endpoints included overall survival (OS) rate, objective response rate (ORR) by RECIST v1.1, and safety. Results: Patients characteristics: 49 pts were eligible for inclusion with median age of 60.7 years old (range 18.0-89.0), 91.8% were ECOG PS 0-1, 86.5% had HBV infection, 79.6% were stage III and 48.9% were AFP&gt;400 ng/ml. 33 pts administrated with combination therapy, other 16 pts’ regimen was icaritin monotherapy. Efficacy: As of the data cutoff for the preliminary analysis of progression free survival (Nov 30, 2023), the median follow-up was 11.17 months (95%CI 6.74–12.12). The ORR for the combination group was 6.06%, and 12.50% for the mono-group, the mPFS was 8.94(95%CI 6.90~9.76) and 5.52 (2.92~NE) for each group. The mOS was not reached for both group, the 6 and 12-months OS rates were 91.00% and 73.67% respectively. Safety: For the safety information, most of TRAEs were grade 1 or 2. No serious AEs were observed. Conclusions: This real-world retrospective study revealed that icaritin monotherapy and icaritin-based combination therapy are promising therapeutic options for unresectable HCC in China. Clinical trial information: ChiCTR2300074565.
Efficacy and safety of disitamab vedotin (RC48) combined with camrelizumab and S-1 for neoadjuvant therapy of locally advanced gastric cancer with HER2 overexpression: Preliminary results of a prospective, single-arm, phase II study.
Authors: Jie Chai, Longgang Wang, Luguang Liu, Bing Liu, Dong Sun
Journal: Journal of Clinical Oncology (2024)

e16100 Background: A combination of HER2-targeted therapy, immunotherapy and chemotherapy is being explored in the perioperative treatment of gastric/gastric junction (GC/GEJ) adenocarcinoma.Disitamab vedotin (RC48), a HER2-directed antibody-drug conjugate (ADC), demonstrated significant anti-tumor activity. Moreover, data suggest that the combination of RC48 with immunotherapy exhibits a synergistic effect. Therefore, we conducted the study to investigate the effects of combining RC48 with camrelizumab and S-1 in the neoadjuvant setting for locally advanced, resectable GC/GEJC with HER2 overexpression. Methods: In this prospective, phase II, single-arm study, we included patients with histologically confirmed, resectable gastric/gastric junction adenocarcinoma (GC/GEJ) staged as cT3-4aN1-3M0 according to the TNM 8th edition, and demonstrating HER2 overexpression (IHC 3+ or IHC 2+). Participants received three cycles of treatment on a three-weekly basis (Q3W). Surgical resection was scheduled to occur 3-4 weeks following the completion of neoadjuvant therapy. The primary endpoint was the pathological complete response (pCR) rate; the secondary endpoints included the major pathological response (MPR) rate, clinical downgrading rate, disease-free survival (DFS), overall survival (OS), and safety. Results: Between Sep 18, 2022 and Feb 2, 2024, a total of 23 patients were enrolled. Seven patients had not completed neoadjuvant treatment.Two patients refused surgery due to organ preservation. Two patients refused study therapy after 2 cycles of neoadjuvant treatment. 12 patients who experienced D2 resection, 6 (50%) achieved MPR, including 4 (33.3%) with pCR (ypT0N0M0).The R0 resection rate was 100%. Median DFS and OS have not been reached. The most common reported AEs (grade≥3) were decreased neutrophil count (10%), bowel obstruction (5%), ALT increased (5%) and AST increased (5%). There have been no treatment-related mortalities documented. Conclusions: The preliminary findings suggest that the neoadjuvant combination of RC48, camrelizumab and S-1 presents a promising and safe treatment option for locally advanced resectable GC/GEJ adenocarcinoma with HER2 overexpression. Clinical trial information: ChiCTR2300075446.
A single-arm exploratory clinical study of β-glucan combined with camrelizumab and SOX chemotherapy as first-line treatment for advanced gastric adenocarcinoma.
Authors: Wenyu Zhu, Yunqian Chu, Xuan He, Hua Jiang, Chan Zhu, Xing Zhang, Fangfang Wu, Hanjue Dai, Qingying Xian, Ya Xue
Journal: Journal of Clinical Oncology (2024)

e16008 Background:The combination of immunotherapy plus chemotherapy has revolutionized the therapy pattern of advanced gastric adenocarcinoma, but the efficacy is still unsatisfactory. β-glucan has been reported to be a potential natural immune modulator for tumor growth inhibition. Therefore, we aimed to evalute the efficacy and safety of β-glucan plus immunotherapy and chemotherapy in the first-line treatment of advanced gastric adenocarcinoma. Methods:This is a prospective, single-arm, investigator-initiated trail. All included patients are adults with advanced gastric adenocarcinoma, and with an Eastern Cooperative Oncology Group (ECOG) score ≤ 2. Eligible patients received WGP β-glucan (500 mg; twice daily on days 1-14) + camrelizumab (day 2; fixed-dose 200 mg) + oxaliplatin (day 1; 130 mg/m2)+ oral S-1 (twice daily on days 1-14; body surface area &lt; 1.25 m2: 40 mg; body surface area 1.25-1.5 m2: 50 mg; body surface area &gt; 1.5 m2: 60 mg) every 3 weeks. The curative effect is evaluated (RECIST 1.1) every 2 cycles. Safety evaluation indicators include vital signs, laboratory indicators and treatment-related adverse events (TRAEs). The primary endpoints were objective response rate (ORR) and safety; the secondary endpoints were median progression-free survival (mPFS) and median overall survival (mOS); the exploratory endpoint treatment-related biomarker changes from liquid biopsies. Results:From April 2021 to October 2022, a total of 30 patients with average of 67.5 years old had been enrolled, incuding 20 (66.7%) males and 8 (26.7%) patients with an ECOG PS score of 2. The ORR was 60%; the mPFS was 10.4 months (95% confidence interval [CI], 9.52-11.27); the mOS was 14.0 months (95% CI, 11.09-16.91). A total of 19 patients (63.3%) had TRAEs, with 9 patients (30%) with grade ≥ 3. The most common treatment-related adverse events were nausea (53.3%) and hemangioma (33.3%). No TRAEs associated with β-glucan were observed. After 2 cycles of treatment, the levels of IL-2 and IFN-γ significantly increased ( P &lt; 0.05), and the number of CD4 + T cells also significantly increased ( P &lt; 0.05). Furthermore, the protein expressions of GZMA, GZMH, and CD244 were significantly lower in the responding group (CR+ PR) than in the non-responding group (SD + PD) (P &lt; 0.05). Conclusions: This preliminary study demonstrates that β-glucan plus camrelizumab and SOX chemotherapy offers favorable efficacy and a manageable safety profile in patients with advanced gastric adenocarcinoma, and further studies are needed to verify its efficacy and safety. Clinical trial information: ChiCTR2100044088.