El Palomar - Morã³n, Argentina

Safety and Efficacy of Cryoablation With Karelizumab and Apatinib for Multiple Lung Cancers

Adjuvant Adebrelimab Plus Apatinib for Participants With HCC at High-risk of Recurrence After Curative Resection

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Surgical resection is the most important radical treatment. However, the recurrence rate is high especially in the participants with high risk of recurrence after curative resection. Adebelimumab is a humanized anti-PD-L1 monoclonal antibody independently developed by Hengrui Pharmaceutical. It can specifically bind to PD-L1 molecules to block the PD-1/PD-L1 pathway that leads to tumor immune tolerance, reactivate the anti-tumor activity of the immune system, and achieve the goal of treating tumors. As of October 8, 2021, adebelimumab has conducted several clinical studies in various malignant tumor fields and has shown good anti-tumor efficacy and controllable safety. Therefore, the investigators plan to conduct a prospective clinical study targeting HCC participants at high risk of postoperative recurrence, to demonstrate the efficacy and safety of postoperative adjuvant therapy with adebelimumab combined with apatinib. This study has the potential to provide efficient new treatment options for participants, which is of great significance for improving the survival rate and quality of life of liver cancer participants in general. A mid-term analysis will be conducted on the recurrence free survival rate and survival rate, at 6 months after the enrollment of 30 participants.

BIOmarker Driven Trial of VEGFR2 Inhibitor in Advanced or Metastatic Sarcoma

After standard chemotherapy and surgery for the localized disease, pulmonary metastases of bone and soft tissue sarcoma occurs in up to 40% of cases and still remain challenging without satisfactory regimen. Apatinib has been reported as a novel oral kinase inhibitor of receptor tyrosine (TKI) targeting VEGFR2 as an angiogenesis inhibitor. Previous studies indicated that Apatinib, as well as other novel VEGFR inhibitor (such as Regorafenib, Cabozantinib, Pazopanib ), showed a promising anti-sarcoma activity with a 4 month progression free rate (PFR) ranging from 40 to 60% in advanced bone and soft tissue sarcoma after multi-line chemotherapy failure. However, the significant inter-individual variability of the agents suggests a lack of predictive biomarker for its clinical use. Furthermore, up to 10~30% of patients may encounter pneumothorax, a potentially life-threatening consequence. Other common debilitating adverse effects (AEs) include surgical wound complication, hand foot skin reaction, etc. Our preliminary data (Presented in ESMO poster session and ESMO Asia oral session in 2019) suggests that rs2071559_VEGFR2 604A>G polymorphism is associated pulmonary tumor cavitation (predisposes one to pneumothorax), hair depigmentation, superior anti-tumor efficacy. Therefore, the investigators aim to explore the clinical signficance of pneumothorax incidence as well as the efficacy of Apatinib monotherapy for advanced bone and soft tissue sarcoma in association with VEGFR-2 (KDR) 604 genotype. We aim to further conduct our clinical study in two cohorts: the observational study cohort and the prospective clinical trial cohort. In the observational cohort, we recruited patients with anti-angiogenic TKIs who encounter pneumothorax during the course of the treatment from nation-wide as a real world study. We review the radiological features of their tumor (such as cavitation, location, etc.) and the medical history of the pre-treatment. We then prospectively follow up the oncological outcomes and the respiratory outcomes given that all pneumothoraces are treated with multidisciplinary approaches to minimize the adverse effect of pneumothoax and maximize the duration of response to anti-angiogenic TKIs. We expect that the patients with pneumothorax (an efficacy related toxicity), if managed actively, will have a durable progression-free survival compared to historical control. Blood samples will also be collected for genotyping VEGFR2 604A>G polymorphism status as a validation to our preliminary findings. In the prospective clinical trial cohort, we formally designed a prospective single-arm, open-label, biomarker-driven phase II clinical trial to explore the efficacy of Apatinib, a novel anti-angiogenic oral inhibitor, in biomarker-based selective patients as follows: With all comers(biomarker positive and negative) allowed to be enrolled, only VEGFR-2 (KDR) 604A>G polymorphism positive will be measured for the primary endpoint of the study according to our sample size estimation . The primary objective is to hypothesize that the progression-free rate (PFR) of Apatinib in this population is ≥ 70% at 4 months (tremendous higher than non-biomarker driven historical control), against the null hypothesis of PFR ≤ 50% as in the general sarcoma patients. Using Simon's two stage design, we are going to recruit 9 biomarker-positive patients in the first stage. If the primary objective was reached in >3 patients, study continue to recruit a total of 28 biomarker-positive patients. The primary endpoint will be considered met if 18 or more patients achieve PFR at 4 months. Considering the potential lost to follow-up, a total of 30 patients with biomarker positive is needed in this trial. Biomarker-negative patients will be analyzed as a non-comparative control without pre-specified sample size, which is expected to be similar to the historical control of advanced bone and soft tissue sarcoma.

Apatinib in the Treatment of Recurrent Atypical/malignant Meningioma in Adults

Vascular endothelial growth factor VEGF is related to the abnormal angiogenesis of meningioma and can also activate other growth factor pathways. Meningiomas are vascular tumors. Studies have shown that the expression of VEGF in atypical meningiomas is twice that of benign meningiomas, and VEGF in anaplastic meningiomas is 10 times that of benign meningiomas. Therefore, anti-angiogenesis therapy may be more effective for higher grade meningiomas. Previous clinical studies have confirmed that anti-angiogenic drugs such as bevacizumab, sunitinib and PTK 787 can slow down tumor growth and prolong progression-free survival for recurrent atypical/malignant meningioma. In summary, apatinib mesylate may be an effective treatment for recurrent atypical/malignant meningioma. This prospective clinical study is now planned to verify the effectiveness and safety of apatinib mesylate in the treatment of relapsed atypical/malignant meningioma.

Camrelizumab in Combination With Apatinib and Temozolomide as First-line Treatment in Advanced Acral Melanoma

A Real-world Study of Camrelizumab Alone or in Combination With Apatinib/Chemotherapy for Advanced Gastric Cancer

PD-1 Antibody Carilizumab Combined with Apatinib for Unresectable Stage III and IV DMMR Gastric Cancer

This study is a prospective, open label, single center, phase II clinical trial aimed at evaluating the safety and efficacy of PD-1 antibody Carilizumab combined with apatinib for the conversion therapy of unresectable stage III and IV dMMR gastric cancer. The study participants were unresectable stage III and IV dMMR gastric cancer patients who had not undergone any anti-tumor treatment. The study aims to enroll 20 participants with a primary endpoint of 1-year disease progression free survival rate. participants who meet the inclusion criteria will receive treatment with both Carilizumab and Apatinib, repeated every 21 days. During the conversion therapy period, the researchers evaluate whether surgery can be performed after every 2 cycles of medication for the subjects. After evaluation by the researchers, the participants were deemed eligible for surgery. Apatinib was discontinued for one cycle and an additional course of Carilizumab was administered in preparation for surgery. The time between the last dose and surgery was 3-6 weeks, with a maximum of 6 weeks. Both surgical and non-surgical subjects will continue to receive treatment with the original regimen of Carilizumab combined with Apatinib after surgery until disease progression, recurrence, or death, for a maximum of 2 years. After the treatment is completed, a treatment end visit, a post treatment safety visit, and survival follow-up will be conducted. Participants who end the study due to non disease progression reasons will undergo imaging evaluation at the end of treatment (if no imaging evaluation has been received within 4 weeks before the end of treatment), and imaging evaluation will be conducted every 2 months after the end of treatment to assess the time of disease progression. After the completion of treatment, the participants will undergo a survival follow-up every 90 days to collect and record their survival status and subsequent anti-tumor treatment.

Apatinib Combined With Camrelizumab in Treating Participants With Advanced Chordoma

PRIMARY OBJECTIVES: I. To assess the clinical benefit of the combination of Camrelizumab combined with Apatinib in patients with advanced chordomas by adverse events (AEs) and progression free survival (PFS). SECONDARY OBJECTIVES: I. Ascertain the safety of nivolumab in combination with relatlimab in subjects with metastatic or locally advanced/unresectable chordoma by the Overall survival (OS), objective response rate (MPR) and disease control rate (DCR) EXPLORATORY OBJECTIVES: I. Compare response rate (RR) and clinical benefit rate (CBR) in patients whose tumors are PD-L1+ and PD-L1- at baseline. II. Compare RR and CBR in patients whose tumors are VEGFR+ and VEGFR- at baseline. III. In the patients who are PD-L1 positive, compare RR and CBR in patients with 1% and 5% tumor membrane staining. III. Determine the response to treatment based on the baseline mutation load. IV. Determine the ORR and CBR via Choi criteria. OUTLINE: To evaluate the safety and tolerability of carrilizol combined with apatinib in patients with recurrent, unresectable, chemotherapy-failed chordoma After completion of study treatment, participants are followed up within 3 months.

Adebrelimab Plus Apatinib and Etoposide for the Treatment of HER2-Negative Breast Cancer Brain Metastasis

Perioperative Treatment of Resectable Intrahepatic Cholangiocarcinoma With the Combination of Adebrelimab and Apatinib and HAIC