Real-world clinical outcomes in avelumab-treated patients (pts) in the United States (U.S.) from SPEAR-Merkel –Study informing treatment Pathway dEcisions in Merkel cell cARcinoma (MCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22029-e22029
Author(s):  
Charles Lance Cowey ◽  
Frank Xiaoqing Liu ◽  
Ruth Kim ◽  
Marley Boyd ◽  
Nicole Fulcher ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Outcomes ◽  
Real World ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
The United States ◽  
Emergency Department Visits ◽  
Sample Population ◽  
Clinical Trial Information

e22029 Background: MCC is a rare, aggressive disease associated with poor prognosis. Avelumab, a fully human anti–PD-L1 monoclonal antibody, was the first immune checkpoint inhibitor approved by the FDA for the treatment of metastatic MCC (mMCC). In the JAVELIN Merkel 200 trial (Clinical trial information: NCT02155647), avelumab resulted in durable responses and a high objective response rate (ORR) in pts with mMCC. This retrospective descriptive study assessed real-world clinical outcomes in avelumab-treated pts with locally advanced MCC (laMCC) and mMCC in a US community oncology setting. Methods: This study included data on avelumab-treated laMCC and mMCC pts from 1/1/17 to 3/31/19 within The US Oncology Network. Study data were captured through 9/30/19 using structured fields and chart review of iKnowMed electronic healthcare records. Real-world ORR was assessed. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Results: 33 pts initiated treatment with avelumab (laMCC n = 11; mMCC n = 22) and were followed up for a median of 10.9 months (range, 0.5-27.2 months). Median age was 77 years (range, 44-90+ years), 78.8% of pts were male, and the majority (84.8%) of pts were treated in the first-line setting. During treatment, 27.2% of pts had emergency department visits and 39.4% were hospitalized; 1% and 23.1%, respectively, were treatment related. Clinical outcomes are reported in the table. Conclusions: This is the first study to examine pts with laMCC treated with avelumab in a real-world setting. Although the sample population is small, results suggest the clinical benefits in the real world in pts with mMCC treated with avelumab are consistent with benefits reported in the JAVELIN Merkel 200 trial. Clinical trial information: NCT02155647 . [Table: see text]

Real-world clinical outcomes in avelumab-treated patients (pts) in the United States (U.S.) from SPEAR-Merkel: Study informing treatment pathway decisions in Merkel cell carcinoma (MCC).

2020 ◽  
Vol 38 (29_suppl) ◽  
pp. 269-269
Author(s):  
Abhijeet Bhanegaonkar ◽  
Frank Xiaoqing Liu ◽  
Ruth Kim ◽  
Marley Boyd ◽  
Nicole Fulcher ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Real World ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
The United States ◽  
Study Data ◽  
Emergency Department Visits ◽  
Sample Population ◽  
Line Setting

269 Background: MCC is a rare, aggressive disease associated with poor prognosis. Avelumab, a fully human anti–PD-L1 monoclonal antibody, was the first immune checkpoint inhibitor approved by the FDA for the treatment of metastatic MCC (mMCC). In the JAVELIN Merkel 200 trial (Clinical trial information: NCT02155647), avelumab resulted in durable responses and a high objective response rate (ORR) in pts with mMCC. This retrospective descriptive study assessed real-world clinical outcomes in avelumab-treated pts with locally advanced MCC (laMCC) and mMCC in a US community oncology setting. Methods: This study included data on avelumab-treated laMCC and mMCC pts from 1/1/17 to 3/31/19 within The US Oncology Network. Study data were captured through 9/30/19 using structured fields and chart review of iKnowMed electronic healthcare records. Real-world ORR was assessed. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Results: 33 pts initiated treatment with avelumab (laMCC n = 11; mMCC n = 22) and were followed up for a median of 10.9 months (range, 0.5-27.2 months). Median age was 77 years (range, 44-90+ years), 78.8% of pts were male, and the majority (84.8%) of pts were treated in the first-line setting. During treatment, 27.2% of pts had emergency department visits and 39.4% were hospitalized; 1% and 23.1%, respectively, were treatment related. Clinical outcomes are reported in the table. Conclusions: This is the first study to examine pts with laMCC treated with avelumab in a real-world setting. Although the sample population is small, results suggest the clinical benefits in the real world in pts with mMCC treated with avelumab are consistent with benefits reported in the JAVELIN Merkel 200 trial. [Table: see text]

scholarly journals Real-world clinical outcomes with first-line avelumab in locally advanced/metastatic Merkel cell carcinoma in the USA: SPEAR-Merkel

2021 ◽  
Author(s):  
Charles Lance Cowey ◽  
Frank X Liu ◽  
Ruth Kim ◽  
Marley Boyd ◽  
Nicole Fulcher ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Merkel Cell Carcinoma ◽  
Real World ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Response Rates ◽  
Merkel Cell ◽  
First Line ◽  
The Usa

Aim: To assess clinical outcomes in patients with locally advanced (la) or metastatic (m) Merkel cell carcinoma (MCC) initiating first-line (1L) avelumab in a USA community oncology setting. Materials & methods: Adults with laMCC or mMCC initiating 1L avelumab were identified from The US Oncology Network electronic health record database and chart review. Results: Median overall survival and progression-free survival were not reached in laMCC (n = 9) vs 20.2 and 10.0 months in mMCC (n = 19); response rates were similar (66.7% vs 63.2%). Conclusion: This is the first study to show clinical benefit in patients with laMCC receiving 1L avelumab in a US real-world setting. Response rates in patients with mMCC were consistent with pivotal trials.

A real-world study of camrelizumab in the treatment of hepatocellular carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16121-e16121
Author(s):  
Yong-Yi Zeng ◽  
Wu-hua Guo ◽  
Zhibo Zhang ◽  
Xi Shi ◽  
Yongjie Su ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Real World ◽  
Group Performance ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Chinese Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase Ii Studies ◽  
Clinical Trial Information

e16121 Background: Programmed cell death protein‐1(PD-1) targeted immunotherapy is a promising treatment strategy for advanced hepatocellular carcinoma. Anti-PD-1 inhibitor camrelizumab showed antitumour activity in phase II studies of advanced hepatocellular carcinoma, with manageable toxicities. This study evaluates safety and efficacy of camrelizumab in patients with advanced hepatocellular carcinoma. Methods: This is a multicentre, real‐world trial done at thirty-three centres in Fujian Province, China. Eligible patients were aged 18 to 75 years was diagnosed by China Liver Cancer Staging(CNLC) 2019 clinical diagnostic criteria or with a histological or cytological diagnosis of advanced hepatocellular carcinoma, unresectable or had progressed on or were intolerant to previous systemic treatment, and had an Eastern Cooperative Oncology Group performance score of 0-1. Patients were received camrelizumab 200 mg intravenously every 2 weeks plus other treatments, such as molecular targeted drug, transcatheyer artetial chemoembolization, radiotherapy and chemotherapy. The primary endpoints were progression-free survival. Safety was analysed in all treated patients. Follow-up is ongoing. Results: Between Mar 12, 2020, and Dec 25, 2020, 63 patients were screened for eligibility, of whom 41 eligible patients received camrelizumab were recruited and among whom 15 received apatinib, 16 received lenvatinib, 2 received sorafenib and 1 received regorafenib. Median followup was 5.28 months (IQR 1.63–10.20). Objective response was reported in 12 (29.3%; 95% CI 16.1–45.5) of 41 patients. Disease control was reported in 34 (82.9%; 95% CI 67.9–92.8) of 41 patients. The median PFS was not reached, and expected more than 9 months. Grade 3 or 4 treatment-related adverse events occurred in 21 (51.2%) of 41 patients; the most common were increased gamma-glutamyltransferase (15 [36.6%]) and increased aspartate aminotransferase (7 [17%]). One death was judged by the investigators to be potentially treatment-related (due to upper gastrointestinal bleeding). Conclusions: Camrelizumab showed promising efficacy and safety in pretreated Chinese patients with advanced hepatocellular carcinoma, and might represent a new treatment option for these patients. Clinical trial information: ChiCTR2000041405. Research Sponsor: Jiangsu Hengrui Medicine Co., Ltd. Clinical trial information: ChiCTR2000041405.

scholarly journals CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer

2018 ◽  
Vol 36 (28) ◽  
pp. 2836-2844 ◽  
Author(s):  
Yelena Y. Janjigian ◽  
Johanna Bendell ◽  
Emiliano Calvo ◽  
Joseph W. Kim ◽  
Paolo A. Ascierto ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Esophagogastric Cancer

Purpose Metastatic esophagogastric cancer treatments after failure of second-line chemotherapy are limited. Nivolumab demonstrated superior overall survival (OS) versus placebo in Asian patients with advanced gastric or gastroesophageal junction cancers. We assessed the safety and efficacy of nivolumab and nivolumab plus ipilimumab in Western patients with chemotherapy-refractory esophagogastric cancers. Patients and Methods Patients with locally advanced or metastatic chemotherapy–refractory gastric, esophageal, or gastroesophageal junction cancer from centers in the United States and Europe received nivolumab or nivolumab plus ipilimumab. The primary end point was objective response rate. The association of tumor programmed death-ligand 1 status with response and survival was also evaluated. Results Of 160 treated patients (59 with nivolumab 3 mg/kg, 49 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, 52 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg), 79% had received two or more prior therapies. At the data cutoff, investigator-assessed objective response rates were 12% (95% CI, 5% to 23%), 24% (95% CI, 13% to 39%), and 8% (95% CI, 2% to 19%) in the three groups, respectively. Responses were observed regardless of tumor programmed death-ligand 1 status. With a median follow-up of 28, 24, and 22 months across the three groups, 12-month progression-free survival rates were 8%, 17%, and 10%, respectively; 12-month OS rates were 39%, 35%, and 24%, respectively. Treatment-related grade 3/4 adverse events were reported in 17%, 47%, and 27% of patients in the three groups, respectively. Conclusion Nivolumab and nivolumab plus ipilimumab demonstrated clinically meaningful antitumor activity, durable responses, encouraging long-term OS, and a manageable safety profile in patients with chemotherapy-refractory esophagogastric cancer. Phase III studies evaluating nivolumab or nivolumab plus ipilimumab in earlier lines of therapy for esophagogastric cancers are underway.

Orally administered CCR2 selective inhibitor CCX872-b clinical trial in pancreatic cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 276-276 ◽  
Author(s):  
Marcus Smith Noel ◽  
Aram F. Hezel ◽  
David Linehan ◽  
Andrea Wang-Gillam ◽  
Ferry Eskens ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Ct Scan ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Receptor Occupancy ◽  
Pancreatic Tumors ◽  
Tumor Control ◽  
Primary Analysis

276 Background: CCR2 inhibition decreases tumor-associated macrophages and Treg cells, and increases CD8+ and CD4+ T cells in pancreatic tumors. Single oral doses of 150 mg CCX872-B were well tolerated in patients with pancreatic cancer. The first stage results of the multiple dose part of this study are presented. Methods: Patients with locally advanced or metastatic pancreatic cancer, ECOG score ≤ 2 were studied. Patients received FOLFIRINOX (fluorouracil [5-FU], leucovorin, irinotecan, oxaliplatin) q2weeks for up to 24 wks plus 150 mg CCX872-B once or twice daily until disease progression or intolerance to CCX872-B. The primary efficacy endpoint is progression-free survival (PFS) at 24 wks. Tumor control rate (TCR) and the objective response rate (ORR), a secondary endpoint, are presented. Results: Fifty patients were enrolled. Baseline: Mean ± SD age: 60 ± 8.6 years, male 52%; primary tumor location: head 57%, body/tail 41%, local recurrence 2%; metastatic disease 78%, ECOG score 0: 62%, ECOG score 1: 38%. Thirty five of 50 patients completed week 12. Most common reasons for early withdrawal were subject request (5 pts) and adverse events typically associated with FOLFIRINOX (4 pts). In the pre-specified analysis population, i.e., those with ≥ 1 post baseline CT scan, tumor control at wk 12 was achieved in 32 of 41 (78%) patients, with 15 of 41 (37%) partial responders, and 17 of 41 (41%) with stable disease. The ORR was 37% (all partial responders) in the primary analysis population (30% when all enrolled patients were included). Thirteen of 21 patients with available CT scan results at week 24 were progression-free. Mean trough CCX872 plasma level was ~8 μg/mL. CCR2 was covered 88% on average by CCX872-B based on receptor occupancy assays. CCX872-B appeared to be well tolerated and the incidence of ≥ Gr 3 AEs was not increased with CCX872-B plus FOLFIRINOX vs historical data with FOLFIRINOX alone. The complete set of PFS data will be available by the end of 2016. Conclusions: CCX872-B plus FOLFIRINOX resulted in a TCR of 78% and an ORR of 30 to 37% with no safety issues ascribed to CCX872-B use. Clinical trial information: NCT02345408.

Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): The phase II AVETUX-CRC trial (AIO KRK 0216).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS3620-TPS3620 ◽  
Author(s):  
Alexander Stein ◽  
Mascha Binder ◽  
Carsten Bokemeyer ◽  
Salah Eddin Al Batran ◽  
Axel Hinke ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Mismatch Repair ◽  
Phase Ii ◽  
Type I Error ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Type I ◽  
Translational Research Program ◽  
Clinical Trial Information

TPS3620 Background: Inhibition of the PD-1/L1 axis has shown to improve survival as single agent in a variety of tumor types. The efficacy of single agent PD-1/L1 inhibition in patients with treatment refractory MCRC seems to be limited to hypermutated tumors characterized by mismatch repair deficiency. 1st line chemotherapy (e.g. FOLFOX) with cetuximab for patients with RAS/BRAF wildtype MCRC result in objective response rates of about 60%, thus substantial antigen release will likely occur triggering immune control. Furthermore, the induction of immunogenic cell death has been recently shown for cetuximab-based regimen. Thus, the evaluation of FOLFOX and cetuximab in combination with avelumab in 1st line MCRC is of particular interest. Methods: AVETUX is a single arm exploratory phase II investigator initiated trial. Patients with RAS/BRAF wildtype MCRC will be included independent of mismatch repair status to receive mFOLFOX6 and cetuximab in combination with avelumab (10mg/kg from day 1 of cycle 2 onwards). Treatment with avelumab is limited to a maximum of 18 months. Primary endpoint is 12month progression-free survival rate, which should be increased from 40% to 57%, with type I error of 10% and 80% power, leading to a sample size of 43 patients. An early stopping rule will be applied in case of an increase in toxicity after the first 15 patients received at least two months of treatment. The trial is flanked by a large translational program including immunoprofiling to determine and correlate the respective immune response signatures with clonal dynamics (RAS/EGFR). Recruitment will start in 11 German sites early 2017. Clinical trial information: EudraCT No 2016-004434-26. Conclusion: The AVETUX trial will determine the feasibility and early efficacy of FOLFOX and cetuximab combined with avelumab in 1st line MCRC. The translational research program will shed light on the potential mode of action of this novel combination. Clinical trial information: 2016-004434-26.

Prospective, multicenter, noninterventional and registry clinical study of apatinib in patients with advanced gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 137-137 ◽  
Author(s):  
Chunmei Bai ◽  
Diansheng Zhong ◽  
Ruixing Zhang ◽  
Xiubao Ren ◽  
Likun Liu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Phase Iii ◽  
Efficacy Evaluation ◽  
Real World Data ◽  
Skin Reactions

137 Background: The aim of this study was to observe the safety of apatinib in the real world with wider inclusion criteria. The efficacy of apatinib was evaluated including overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Methods: This trial enrolled patients from 32 centers in china with advanced gastric adenocarcinoma who had progressed after undergoing at least two lines of systemic chemotherapy, or patients who were considered to benefit from the treatment. We recommended starting from oral administration of 500mg qd, 28 days for a cycle. Dose could be appropriately adjusted according to the patients’ physical condition. Results: Between March 2015 and September 2017, 326 patients were enrolled. The average age was 62 years old, and the ratio of male to female was about 2:1. Patients received perioperative, first-line, second-line, and third-line or more treatment were 1,39,69 and 217 people respectively. There were 192 patients received efficacy evaluation, 9 patients achieved partial response(PR), 125 had disease stability(SD). The ORR and DCR were 4.6% and 69.8% respectively. The median PFS and median OS were 3.7 months and 7.3 months respectively. In the 326 patients, there were 153 patients with initial dose of 500 mg, 3 and 55 patients achieved PR and SD, respectively. The ORR and DCR were 3.3% and 63.7%, respectively. The median PFS and median OS were 3.5 months and 8.4 months, respectively. There were 237 patients in all 326 patients received safety analysis. Common adverse events were hypertension (57%), hand-foot skin reactions (26.6%), fatigue (29.5%), proteinuria (19.0%), bleeding (10.1%) and diarrhea (8.0%). The grade 3 to 4 adverse events were hypertension (6.3%), hand-foot skin reactions (3.8%), proteinuria(3.0%) and bleeding (2.1%). Conclusions: This real-world data in which more patients were given apatinib 500mg or less qd showed similar efficacy to Phase III clinical trial (850mg qd).The incidence of adverse events was consistent with that of Phase III clinical data,there was no new adverse events had been seen. Clinical trial information: NCT02668380.

A phase 2 prospective trial of cabozantinib as first-line treatment for metastatic collecting ducts renal cell carcinoma: The BONSAI trial (Meeturo 2) clinical trial information—NCT03354884.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4571-4571
Author(s):  
Giuseppe Procopio ◽  
Pierangela Sepe ◽  
Sebastiano Buti ◽  
Melanie Claps ◽  
Maurizio Colecchia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Primary Endpoint ◽  
Molecular Subtypes ◽  
Objective Response ◽  
Prospective Trial ◽  
Progression Free Survival ◽  
Overall Response ◽  
Collecting Ducts ◽  
Immune Related Genes ◽  
Clinical Trial Information

4571 Background: Metastatic collecting ducts carcinoma (mCDC) is a rare disease with bad prognosis and no standard treatments. Due to its rarity, mCDC is biologically poorly characterized and under-represented in prospective randomized trials. We recently identified two different molecular subtypes of mCDC based on relative expression levels of angiogenesis, metabolic and immune-related genes. Methods: : This prospective, monocentric, phase II trial evaluated cabozantinib (cabo) 60 mg orally once daily until progression or unacceptable toxicity in untreated mCDC patients (pts). Primary endpoint was objective response rate (ORR) as the proportion of pts with best overall response of confirmed complete (CR) or partial responses (PR) per RECIST 1.1. Secondary endpoints were progression-free survival (PFS), overall survival and safety profile. Exploratory objectives were: to identify somatic mutations by targeted NGS-based sequencing; to define molecular subtypes, signatures and transcript fusions genes by RNA sequencing; to monitor circulating immune cells and study the immunological context of tumor cells. A central pathological review was mandatory. The study was based on a Simon’s two stage optimal design: at least 2 responses in 9 pts in the first stage were needed to proceed to the second stage where at least 6 responses in 14 additional pts were needed to prove activity of cabo. Results: From January 2018 to November 2020, 25 pts were enrolled, of whom 23 started treatment. Median age was 66 years, 19 pts were male. 19 (83%) pts received a previous nephrectomy. 9 pts presented with only one metastatic site, 8 pts with two, while the remaining part with multiple sites. The most common metastatic sites were lymphnodes and bone (15 and 13 pts respectively), followed by lung and liver (10 and 4 pts respectively). Median follow up was 8 months. As best overall response, 6 pts presented a stable disease (26%),1 pt achieved a confimed CR and 7 a PR for an ORR of 35%. Median PFS was 6 months. Treatment was feasible and well tolerated. All pts reported at least one grade (G) 1-2 adverse event (AE): the most common were fatigue (43%), hypotiroidism (28%), stomatitis (28%), anorexia (26%), Hand-Foot Syndrome (13%), hypertension (17%), and diarrhea (13%). 5 pts reported G3 AEs (2 thromboembolic events, 2 arterial hypertension, 1 fatigue), while no G4-5 AEs were reported. 17% of pts required dose reduction. DNA sequencing on CDC showed to be feasible, finding 256 mutations in 119 genes (missens mutations the majority). Altered genes, molecular subtypes and signatures will be associated to different outcomes and responses to cabo. Conclusions: The study met its primary endpoint showing promising efficacy and acceptable tolerability of cabo in mCDC pts. Mature results according to mutational profiles and gene signatures will be presented. Clinical trial information: NCT03354884.

Angiogenic and immunomodulatory biomarkers in axitinib-treated patients (pts) with advanced renal cell carcinoma (aRCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 614-614 ◽  
Author(s):  
Brian I. Rini ◽  
Bernard Escudier ◽  
Danielle Murphy ◽  
Panpan Wang ◽  
Jamal Christo Tarazi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Clinical Outcomes ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Kaplan Meier ◽  
Clinical Trial Information

614 Background: Axitinib (axi) is approved for 2nd-line treatment of aRCC. In AXIS trial, median progression-free survival (PFS) was significantly longer in axi- vs sorafenib (sor)-treated pts (hazard ratio [HR] 0.67, 95% CI 0.54–0.81, P<0.0001). Association between mRNA/miRNA expression and clinical outcomes in a subset of axi- or sor-treated pts from AXIS was assessed. Methods: mRNA/miRNA analyses were performed on archival tumor samples. Expression was summarized for responders (complete and partial response) vs non-responders (stable and progressive disease), and for maximum percent tumor change. PFS and overall survival (OS) were analyzed by Kaplan-Meier. Results: Pt characteristics were similar between axi (n=34) and sor (n=33) arms. Association with outcomes is shown in the Table. A correlation was observed for CD68 protein and mRNA expression in axi-treated pts (R=0.4774 P=0.0043 and R=0.3985 P=0.0196, respectively). Both CXCR4 and TLR3 showed differences between treatment arms and association with PFS. TNFSF10 <median, and CD163, CSF1R and miR-221-5p ≥median were associated with shorter OS with axi vs sor ( P<0.05). Clinical trial information: NCT00678392. Conclusions: Immune-related biomarkers were associated with clinical outcomes in axi/sor-treated aRCC pts. Lower CCR7 expression was associated with better response and OS in axi-treated pts. CXCR4 and TLR3 may be predictive of response to axi. Analysis in a larger cohort is warranted.[Table: see text]

Trastuzumab deruxtecan (T-DXd; DS-8201) in combination with pembrolizumab in patients with advanced/metastatic breast or non-small cell lung cancer (NSCLC): A phase Ib, multicenter, study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS1100-TPS1100
Author(s):  
Hossein Borghaei ◽  
Benjamin Besse ◽  
Aditya Bardia ◽  
Julien Mazieres ◽  
Sanjay Popat ◽  
...  
Keyword(s):  
Topoisomerase I ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
The United States ◽  
Antibody Drug Conjugate ◽  
Free Survival ◽  
Phase Ib ◽  
Her2 Breast Cancer

TPS1100 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and potent topoisomerase I inhibitor. In a phase II trial in patients (pts) with heavily pretreated, metastatic HER2+ breast cancer (BC), T-DXd had a confirmed objective response rate (cORR) of 60.9% (112/184) and median progression-free survival (PFS) of 16.4 mo (Modi N Engl J Med 2019); these results led to the recent FDA approval for HER2+ unresectable or metastatic BC after ≥ 2 prior anti-HER2 based regimens. For HER2-low BC and HER2-expressing/mutated NSCLC, no HER2-directed therapies have been approved. In a phase I trial of T-DXd in pts with HER2-low BC or HER2-expressing/mutated NSCLC, cORR was 44.2% (19/43) (Modi SABCS 2018), and 55.6% (10/18) (Tsurutani Thorac Oncol 2018), respectively. In preclinical models, T-DXd combined with an anti–PD-1 antibody was more effective than monotherapy with either agent (Iwata Mol Cancer Ther 2018). Here we describe a phase Ib study of T-DXd in combination with pembrolizumab in pts with locally advanced/metastatic HER2-expressing BC or HER2-expressing/mutated NSCLC (DS8201-A-U106; NCT04042701). Methods: This is an open-label, multicenter, nonrandomized, multidose, 2-part study in adult (aged ≥18 y) pts in the United States and Europe. In part 1 (dose escalation), pts received T-DXd 3.2 or 5.4 mg/kg IV q3w and pembrolizumab 200 mg IV q3w to determine the recommended dose for expansion (RDE). The RDE will be given to 4 cohorts (part 2): 2 cohorts with BC (HER2+ [IHC 3+ or IHC 2+/ISH+] with progression on prior T-DM1; and HER2-low [IHC 1+ or IHC2+/ISH-] with progression on prior standard treatments) and 2 cohorts with NSCLC (anti–PD-1, –PD-L1, and -HER2 treatment naive either HER2-expressing [IHC ≥ 1+] or HER2-mutated). Enrollment began in February 2020 with approximately 115 to 133 pts planned to be enrolled at 5 sites for part 1 and expanding to 25 sites for part 2. The primary endpoint in part 1 is dose-limiting toxicities. The part 2 primary efficacy endpoint is cORR by independent central review (ICR) per RECIST 1.1. Additional endpoints include duration of response, disease control rate, and progression-free survival by ICR, overall survival, safety, and pharmacokinetics. Clinical trial information: NCT04042701 .

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