Happy ASCO abstract day
1 SHR-1210 from Hengrui Medicine
患者选择：三线治疗、EGFR 突变占多数
双臂：确定apa剂量，250mg qd well-tolerated
ORR was 41.2% (arm 1: 30.8%, 4/13; arm 2: 75%, 3/4) and DCR was 94.1% (arm 1: 92.8%, 12/13; arm 2: 100%, 4/4). The median PFS was 24 weeks in arm 1 and not reached in arm 2.
治疗相关SAE（17.8%）：1 fever, 1 upper gastrointestinal hemorrhage, 1 pain, 1 infection reaction, and 1 pneumonia，好像没提那个什么.
A phase Ib study of SHR-1210 plus apatinib for heavily previously treated advanced non-squamous non-small cell lung cancer (NSCLC) patients.
Citation:
J Clin Oncol 36, 2018 (suppl; abstr e21017)
http://abstracts.asco.org/214/AbstView_214_219215.html
Background: SHR-1210 is a selective, humanized, high-affinity IgG4-kappa monoclonal antibody against PD-1. Our preclinical data demonstrated a synergistic anti-tumor effect in vivo with simultaneous blockade of VEGF/VEGFR2 and PD-1/PD-L1 pathways. This phase Ib study was conducted to evaluate the safety, tolerability and activity of SHR-1210 plus apatinib for heavily previously treated advanced non-squamous NSCLC patients.
Methods: 27 patients after failure of more than 2 lines of systemic therapies were treated with SHR-1210 at a dose of 200mg Q2w in combination with apatinib at a dose of 250mg qd (arm 1) or 375mg qd (arm 2) up to disease progression or intolerable toxicity. Primary endpoint was safety and tolerability and key 2nd endpoints were response rate and PFS.
Results: At the cut-off data (Jan. 29. 2018), 27 patients were enrolled (arm 1: 15 patients; arm 2: 12 patients). Median age 58 years old (36-69), M/F: 23/4; Adenocarcinoma/other: 25/2; stage IV 100%; EGFR mutant/wild-type/unknown: 23/2/2. The median treatment duration of SHR-1210 was 22 weeks (range, 4-40 weeks) and apatinib was 24 weeks (range, 1-36 weeks). Dose adjustments were mainly due to apatinib, 2patients interrupted SHR-1210 treatment in arm 1 and 4 patients interrupted SHR-1210 treatment in arm 2. The dose in arm 1 was well tolerated with 1 case developing bronchial-pleural fistula and 1 case anorexia. In arm 2, 4 cases developed grade 3 skin rash, 2 grade 3 hypertension, and 5 patients needed dose reduction to 250mg. Treatment-related SAE occurred in 4 patients (14.8%), including 1 fever, 1 upper gastrointestinal hemorrhage, 1 pain, 1 infection reaction, and 1 pneumonia. 17 patients were included in efficacy analysis. The overall ORR was 41.2% (arm 1: 30.8%, 4/13; arm 2: 75%, 3/4) and DCR was 94.1% (arm 1: 92.8%, 12/13; arm 2: 100%, 4/4). The median PFS was 24 weeks in arm 1 and not reached in arm 2.
Conclusions: SHR-1210 in combination with apatinib at a dose of 250mg was well-tolerated with promising anti-tumor effect, even in heavily previously treated NSCLC patients. The dose of 250mg apatinib + SHR 1210 was recommended in the ongoing phase II trial (ClinicalTrials: NCT03083041).
2 IBI304 from Innovent Biologics ：HL二期单臂(ORIENT-1 study)
74.0% ORR and 24.0% CR rate
TRAE主要 1-2级pyrexia，一般一天后消失
Sintilimab (IBI308) in relapsed/refractory classical Hodgkin lymphoma: A multicenter, single-arm phase 2 trial in China (ORIENT-1 study).
Citation:
J Clin Oncol 36, 2018 (suppl; abstr 7536)
Background: Classical Hodgkin’s lymphoma (cHL), characterized by chromosome 9p24.1 alteration and PD-1 ligands overexpression, is sensitive to PD-1/PD-L1 blockage in previous studies. This study will confirm the efficacy and safety of sintilimab (IBI308), a promising anti-PD-1 monoclonal antibody, in Chinese patients with relapsed/refractory (R/R) cHL.
Methods: ORIENT-1 (NCT03114683) is a multicenter, single-arm, phase 2 study. Patients who failed 2 or more lines of systemic therapy, including autologous hematopoietic stem cell transplantation (HSCT) were enrolled. Sintilimab was given 200 mg intravenously every 3 weeks, until disease progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) according to 2007 IWG criteria. The cut-off date for this analysis was Feb 8, 2018.
Results: Among 96 treated patients enrolled between Mar 30th 2017 and Nov 1st 2017, the median number of previous chemotherapies was 3 (range: 1~13). 54.2% patients received prior radiotherapy and 18.8% failed HSCT. With median treatment cycles of 9 (range: 1~14), ORR was 74.0% (71/96, 97%CI: 64.2%, 83.7%) per IRRC review. 23 patients (24.0%) achieved complete response (CR). The median duration of response has not been reached. At the time of analysis, 64 of 71 complete and partial response patients had an on-going response. The most common treatment-related adverse event (TRAE) was pyrexia (43.8%, 42/96), and 92.9% were grade 1~2. Most of pyrexia happened in the day of first infusion and recovered within 1 day. Other common TRAEs were hypothyroidism (13.5%) and TSH increase (11.5%), and all were grade 1~2. The most common grade 3~4 TRAEs were pyrexia (3.1%) and thrombocytopenia (2.1%). No patient died.
Conclusions: Till now, ORIENT-1 study is the largest cHL study in China. Patients in our study were sensitive to sintilimab, with 74.0% ORR and 24.0% CR rate. The safety profile was consistent with the findings of other anti-PD-1 monoclonal antibodies in cHL patients. Sintilimab could be a new treatment option for R/R cHL patients in China.
Clinical trial information: NCT03114683
补充材料
对比KEYNOTE-087
Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma.
Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response ≥ 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.
对比CheckMate 205
Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial.
Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)-naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C). All patients received nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary end point was objective response rate per independent radiology review committee. Results Overall, 243 patients were treated; 63 in cohort A, 80 in cohort B, and 100 in cohort C. After a median follow-up of 18 months, 40% continued to receive treatment. The objective response rate was 69% (95% CI, 63% to 75%) overall and 65% to 73% in each cohort. Overall, the median duration of response was 16.6 months (95% CI, 13.2 to 20.3 months), and median progression-free survival was 14.7 months (95% CI, 11.3 to 18.5 months). Of 70 patients treated past conventional disease progression, 61% of those evaluable had stable or further reduced target tumor burdens. The most common grade 3 to 4 drug-related adverse events were lipase increases (5%), neutropenia (3%), and ALT increases (3%). Twenty-nine deaths occurred; none were considered treatment related. Conclusion With extended follow-up, responses to nivolumab were frequent and durable. Nivolumab seems to be associated with a favorable safety profile and long-term benefits across a broad spectrum of patients with relapsed/refractory cHL.
3 JS001 from Junshi Biosciences
Preliminary results from patients with metastatic urothelial carcinoma (UC) in a phase 2 study of JS001, an anti-PD-1 monoclonal antibody.
Background: Monoclonal antibodies (mAb) against programmed cell death-1 (PD-1) have demonstrated antitumor activity across multiple malignancies. JS001 is a humanized IgG4 mAb against programmed death-1 (PD-1) . Previous phase 1 study show the clinical activity in metastasis urothelial carcinom. This study is a phase 2 study to evaluate the safety and efficacy of JS001 in patients with metastatic urothelial carcinom.
Methods: This multi-center, open-label, phase II registration study is designed to evaluate safety and efficacy of JS001 in advanced and metastatic urothelial carcinom patients who have failed systemic treatment. JS001 is given at 3 mg/kg IV Q2W until disease progression or intolerable toxicity. Safety and tolerability was assessed by monitoring adverse events (AEs) and antitumor effects were assessed by RECIST v1.1 criteria and irRECIST criteria. Other objectives include immunogenicity and tumor tissue biomarkers.
Results: Enrollment began in May 2017. As of February 10, 2018, 33 patients was enrolled. The most common treatment related AEs were grade 1/2, including ALT increase, hyperglycemia , amylase increase, anemia, AST increase and hypothyroidism.Among 27 evaluable patients, no patient have complete response, 8 patients have partial response, and 13 pts achieve stable disease, for an ORR of 29.6% and a DCR of 77.8%.
Conclusions: JS001 might benefit for metastatic urothelial carcinom who have failed systemic treatment. More patients will be enrolled in next year.
Clinical trial information: NCT03113266
