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.

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]

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.

A phase III study (APROMISS) of AL3818 (Catequentinib, Anlotinib) hydrochloride monotherapy in subjects with metastatic or advanced synovial sarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11505-11505
Author(s):  
Brian Andrew Van Tine ◽  
Sant P. Chawla ◽  
Jonathan C. Trent ◽  
Breelyn A. Wilky ◽  
Rashmi Chugh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Synovial Sarcoma ◽  
Primary Endpoint ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Phase 3 ◽  
Free Survival ◽  
Grade 3 ◽  
Clinical Trial Information

11505 Background: AL3818 (Catequentinib, Anlotinib) is a novel, orally administered, small molecule tyrosine kinase inhibitor. The primary objective of this Phase 3 study is to evaluate the efficacy of AL3818 monotherapy in patients (pts) with synovial sarcoma (SS) comparing with dacarbazine in randomization setting. Methods: Patients with a diagnosis of synovial sarcoma requiring second line or further line treatment were eligible for enrollment. The regimen was a 21-day cycle with oral AL3818 administered on 14 days on and 7 days off. This phase 3 trial is randomized in 2:1 ratio of AL3818 comparing to dacarbazine with option of crossover after PD of dacarbazine treatment. Progression free survival (PFS) with Log Rank test is the primary endpoint and this trial for SS is currently completed enrolled in US and Italy. Results: Total 79 pts initiated treatment and are evaluable, 52 received AL3818 as treatment arm (T), and 27 received dacarbazine (D) as control arm (C). Arms T/C median ages were 40.5/42.0 years (range: 18-70+) and 20/16 (38.5%/59.3%) were male. Overall, PFS was 2.89 months (95% CI: 2.73 – 6.87) for AL3818 and 1.64 (95% CI: 1.45 – 2.70) for D. The PFS of study met the primary endpoint with a p-value of 0.0015 and a HR of 0.449 (95% CI: 0.270– 0.744). At the month 4, 6, and 12, the percentages of progression free patients for AL3818 were 48.1%, 42.3% and 26.9%; and for D were 14.85%, 11.1% and 3.7%. For grade 3 treatment-related adverse events, 12(23.1%) of pts experienced for AL3818 and 7(25.9%) of pts experienced for D. The most common AL3818 related grade 3 AEs were diarrhea (5.8%) and hypertension (3.8%). Conclusions: This phase III trial demonstrates improved disease control and superior progression free survival for AL3818 vs dacarbazine in advanced SS. In addition, the study further confirms the acceptable benefit-risk profile of AL3818 from the prior randomized Phase 2b soft tissue sarcoma study (NCT02449343). AL3818 is a meaningful treatment option for pts with advanced SS. Clinical trial information: NCT 03016819 Clinical trial information: NCT03016819.

Crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): A European phase II clinical trial–Updated report on progression-free and overall survival.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9066-9066
Author(s):  
Sebastian Yves Friedrich Michels ◽  
Jeremy Franklin ◽  
Bartomeu Massuti ◽  
Martin Sebastian ◽  
Hans-Ulrich Schildhaus ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Primary Endpoint ◽  
Objective Response ◽  
In Situ Hybridisation ◽  
Progression Free Survival ◽  
Fluorescence In Situ Hybridisation ◽  
Eligibility Criteria ◽  
Tp53 Mutations

9066 Background: ROS1 rearrangements are found in 1% of non-small cell lung cancer (NSCLC) patients. Early clinical trials in the US and East Asia have proven the therapeutic efficacy of crizotinib in this subset of patients. EUCROSS is the first prospective European trial to evaluate the acitivity of crizotinib in ROS1-positive lung cancer. Here we present an updated analysis of the investigator-assessed progression-free survival (PFS) and overall survival (OS). Methods: EUCROSS is a multi-centre, single arm phase 2 trial (NCT02183870). Key eligibility criteria: ≥18 years of age, advanced/metastatic lung cancer, centrally confirmed ROS1-rearranged (fluorescence-in situ hybridisation). Treatment with crizotinib was initiated at a dose of 250 mg twice daily. Primary endpoint of the trial: investigator-assessed objective response rate (ORR) in the response-evaluable population (Response Evaluation Criteria in Solid Tumors, version 1.1). Key endpoints of this report: updated PFS and OS and updated molecular characterization of tumour tissue. Results: Thirty-four patients received treatment with crizotinib and were included in the intention-to-treat analysis. Four patients were excluded from the primary endpoint analysis due to violation of eligibility criteria (response-evaluable set, N = 30). Median follow-up period was 44.9 months. At the time of data cut-off for this report 19 patients (63%) discontinued treatment due to progression or death. Investigator ORR was 70% (95% CI, 51–85; 21/30), disease control rate was 90% (95% CI, 73.5-97.9; 27/30) and median PFS was 19.4 months (95% CI, 10.1-31.2). Median OS was not reached, but 24-months-OS probability was 66% (95% CI, 48.3-82.9). Tissue of 18 patients was available for hybrid-capture-based sequencing. Co-occurring genetic aberrations were found in 61% (11/18). TP53 mutations were most frequent (28%; 5/18). PFS (24-months probability, TP53-mut. 0% vs. TP53 wild-type (wt) 61%; p = 0.0219) and OS (24-months, TP53-mut. 40% vs. TP53 wt 83%; p = 0.015) were significantly shorter in TP53-mutant patients. Differences in OS and PFS stratified by number of prior treatment lines (0-1 vs. > = 2), brain metastases (yes vs. no) or CD74-rearrangement ( CD74- ROS1 vs. other fusion type) status were not significant. Conclusions: Updated PFS and OS results show that crizotinib is highly effective in ROS1-rearranged lung cancer. Co-occurring TP53 mutations were associated with a significantly worse outcome. Clinical trial information: NCT02183870.

Phase II clinical trial of novel agent PBI-05204 in patients with metastatic pancreatic adenocarcinoma (mPDA).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 698-698
Author(s):  
Marc Thomas Roth ◽  
Dana Backlund Cardin ◽  
Erkut Hasan Borazanci ◽  
Margaux Steinbach ◽  
Vincent J. Picozzi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Nerium Oleander ◽  
Orthotopic Model ◽  
Open Label

698 Background: Survival statistics for mPDA are dismal and with limited treatment options novel agents are needed to improve disease outcomes. PBI-05204 (Phoenix Biotechnology, Inc., San Antonio, TX) is a modified supercritical carbon dioxide extract of Nerium oleander leaves. Oleandrin, the extract’s major cytotoxic component, has demonstrated anti-tumor activity in various tumor cell lines. In a human PDA orthotopic model, this preparation reduced tumor burden as monotherapy. Pharmacodynamic studies suggest that PBI-05204’s mechanism of action is through inhibition of the PI3k/Akt/mTOR pathway. Methods: A phase II single-arm, open-label study to determine the efficacy of PBI-05204 in patients (pts) with mPDA refractory to standard therapy was conducted. The primary endpoint was overall survival (OS) with the hypothesis that 50% of pts would be alive at 4.5 months. Secondary objectives included safety, progression-free survival (PFS), and overall response rate. Pts received oral PBI-05204 daily until progressive disease (PD), unacceptable toxicity, or pt withdrawal. Radiographic response was assessed every two cycles. Results: Forty-one pts were enrolled; two never received treatment and one was found to have a neuroendocrine tumor after pathological re-evaluation, leaving 38 pts for analysis. Median age at time of enrollment was 65.0 years. The median time from initial diagnosis to treatment was 16.9 months. The primary reason for withdrawal was PD (45.2%). Ten pts were alive at 4.5 months (26.3%) with a mPFS of 56 days (corresponding to first restaging). One objective response (2.6%) was observed for 162 days. Grade ≥3 treatment-emergent adverse events occurred in 63.2% of pts with the most common attributed to drug (all grades) being fatigue (36.8%), vomiting (23.7%), nausea (18.4%), decreased appetite (18.4%), and diarrhea (15.8%). Conclusions: PBI-05204 did not meet its primary endpoint for OS in this study. Recent preclinical data indicate an efficacious role for PBI-05204 against glioblastoma multiforme when combined with chemotherapy, such as temozolomide, and radiotherapy. A randomized Phase II trial is currently being designed. Clinical trial information: NCT02329717.

Sintilimab plus anlotinib as first-line therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16146-e16146
Author(s):  
Xiaofeng Chen ◽  
Wei Li ◽  
Xiaofeng Wu ◽  
Fengjiao Zhao ◽  
Deqiang Wang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Antiangiogenic Agents ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
First Line ◽  
First Line Therapy ◽  
Ecog Ps ◽  
Clinical Trial Information

e16146 Background: The synergic combination of anti-PD-1/PD-L1 and antiangiogenic agents has exhibited as an encourage treatment pattern in aHCC. Multi-targeted antiangiogenic TKIs, such as lenvatinib and sorafenib, are approved for 1st-line treatment of aHCC. Sintilimab, a novel selective anti-PD-1 monoclonal antibody, has demonstrated encouraging clinical activities in aHCC. The trial aims to explore the safety and efficacy of sintilimab plus anlotinib (a TKI against angiogenesis) in aHCC. Methods: This is a single-arm phase 2 study. Eligible Pts with aHCC, BCLC stage C or B (not amenable for surgery and chemoembolization), Child-Pugh scores≤7 and ECOG PS ≤ 1 received 1st-line treatment of sintilimab (200mg, iv, D1) plus anlotinib (12mg, po, QD, D1-14) every 3 wks until disease progression or unacceptable toxicity. Primary endpoints were safety and objective response rate (ORR, per RECIST 1.1), and secondary endpoints included disease control rate (DCR), progression free survival (PFS), duration of response (DOR) and overall survival (OS). Results: As of January 15, 2021, 20 pts were enrolled (males 18 ; median age 56 yrs [range 41-70] ; BCLCB/C: 5/15 ; Child-Pugh A/B7: 19/1 ; HBV infection 20). All pts received at least two cycles of treatments with median cycles 7.5 [range 2-22]. Median follow-up was 12 months [range 3-19]. The most common treatment-related adverse events (TRAEs) were grade 1-2 with thrombocytopenia (45.0%), hand-foot syndrome (40.0%), hypertension (35.0%), increased AST (35.0%), ALT (30.0%), decreased neutrophil count (25.0%), leukopenia (25.0%). 8 pts experienced manageable grade 3 TRAEs, and no grade 4/5. 12 pts required dose reduction of anlotinib (9 pts to 10 mg and 3 to 8 mg). No treatment withdraw caused by TRAEs. ORR was 40.0% (8/20) with 1 CR and 7 PR, 11 pts were SD, and DCR was 95.0% (19/20). Median DoR was not reached. 6m-PFS rate was 66.4% (95%CI: 47.7%-92.5%), immature median PFS was 14.65 months (95%CI: 5.06 -not reached) with 8 events. Conclusions: The combination of sintilimab and anlotinib showed promising clinical activities with manageable toxicity for first line treatment of aHCC. Clinical trial information: NCT04052152. Research Sponsor: Innovent Biologics, Inc., Chia-Tai Tianqing Pharmaceutical Group Co Ltd. Clinical trial information: NCT04052152.

Functional precision medicine in colorectal cancer based on patient-derived tumoroids and in-vitro sensitivity drug testing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15567-e15567
Author(s):  
Lars Henrik Jensen ◽  
Anders Kristian Moeller Jakobsen ◽  
Birgitte Mayland Havelund ◽  
Cecilie Abildgaard ◽  
Chris Vagn-Hansen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Primary Endpoint ◽  
Drug Testing ◽  
Progression Free Survival ◽  
Patient Specific ◽  
Precision Oncology ◽  
Sensitivity Testing ◽  
In Vitro Sensitivity

e15567 Background: Precision oncology based on in-vitro, functional assays has potential advantages compared to the much more common molecular approach, but the clinical benefit is unknown. We here report the results from the largest prospective interventional clinical trial testing the clinical outcome in colorectal cancer patients treated with drugs showing cytotoxic effect in matched patient-derived tumoroids. Methods: This single-center, phase II trial included patients with metastatic colorectal cancer previously exposed to all standard therapies. Specimens from one to three 18-16 G core needle biopsies were manually dissected, enzymatically treated, cultivated, and incubated to form 3D spherical microtumors, i.e. tumoroids. In the assay for in-vitro sensitivity testing, the tumoroids were challenged with single drugs and combinations thereof to determine patient-specific responses. Using tumoroid screening technology (IndiTreat, 2cureX, Copenhagen, Denmark), results were generated by comparing the sensitivity of the individual patient’s tumoroids with a reference panel from other patients. The testing included standard cytostatics and drugs with proven effect in previous early-phase clinical trials, a total of 15 drugs. The primary endpoint was the fraction of patients with progression-free survival (PFS) at two months. Based on placebo arms in randomized last-line trials, a minimal relevant difference of 20% (20% to 40%) was stated. Using Simon's two-stage design, a sample size of 45 patients was calculated with at least 14 PFS at two months (significance 5%, power 90%). Results: Ninety patients were enrolled from 9/2017 to 9/2020. Biopsies from 82 patients were obtained and sent for tumoroid formation of which 44 (54%, 95% CI 42-65) were successful and at least one treatment was suggested. Thirty-four patients initiated treatment according to the response obtained in the drug assays within a median of 51 days from inclusion (IQR 39-63). The primary endpoint, PFS at two months, was met in 17 of 34 patients (50%, 95%CI 32-68). There were no radiological responses. Median PFS was 81 days (95% CI 51-112) and median OS was 189 days (95% CI 103-277). Conclusions: Precision oncology using a functional approach with patient-derived tumoroids and in-vitro drug sensitivity testing seems feasible. The approach is limited by the fraction of patients with successful tumoroid development. The primary endpoint was met, as half of the patients were without progression at two months. Further clinical studies are justified. Clinical trial information: NCT03251612.

Anlotinib combined with pemetrexed and carboplatin as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): ALTER L012.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Naïve ◽  
Nsclc Patients ◽  
First Line Treatment

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.

Eribulin and gemcitabine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A multicenter, single-arm, phase 2-trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11516-11516
Author(s):  
Chang Gon Kim ◽  
Jin-Hee Ahn ◽  
Jeong Eun Kim ◽  
Jee Hung Kim ◽  
Min Kyung Jeon ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Alternative Hypothesis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Histologic Types

11516 Background: Eribulin and gemcitabine have shown encouraging efficacy in soft-tissue sarcoma (STS) as a monotherapy. Here, we evaluated the activity and safety of combined use of eribulin and gemcitabine in two most common histologic types of STS, liposarcoma and leiomyosarcoma. Methods: In this non-randomized, multi-center phase 2 study, patients were included if they had progressive disease after one or two prior chemotherapy including doxorubicin. Patient were given eribulin 1.4 mg/m2 and gemcitabine 1,000 mg/m2 on day1 and day 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks) with null and alternative hypothesis of PFSR12wks≤20.0% and ≥40.0%, respectively. Results: Of 37 patients included, 22 had leiomyosarcoma, and 15 had liposarcoma. At 12-weeks after treatment, 16 and (72.7%) 11 (73.3%) patients in leiomyosarcoma and liposarcoma were progression-free. Overall PFSR12wks was 73.0%, satisfying the primary endpoint. Objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 23.9 weeks, and 88.9 weeks, without any statistical differences according to histologic subtypes. No new safety signals and treatment-related death were observed. Conclusions: Eribulin and gemcitabine showed promising activity and manageable safety profile in patients with STS of liposarcoma and leiomyosarcoma histology. Updated outcomes for ongoing patients will be presented. Clinical trial information: NCT03810976.

Dual immune checkpoint blockade in advanced well-differentiated neuroendocrine tumors, a phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16201-e16201
Author(s):  
Susan Combs Scott ◽  
Ana De Jesus-Acosta ◽  
Chen Hu ◽  
Benjamin Philip Levy ◽  
Valsamo Anagnostou ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Median Duration ◽  
Primary Endpoint ◽  
Response Rate ◽  
Objective Response ◽  
Phase Ii Clinical Trial ◽  
Open Label ◽  
Well Differentiated

e16201 Background: Limited systemic treatment options are available for progressive well-differentiated neuroendocrine tumors (NET), also called carcinoid tumors. Given emerging evidence for immunotherapy response in high grade NET including small cell lung cancer, we sought to determine the efficacy of combination immunotherapy with ipilimumab and nivolumab in patients with advanced, progressive, well-differentiated NET in an open label phase II clinical trial. Methods: Eligible patients had well-differentiated, nonfunctional NET of lung, pancreas, or GI origin that had progressed within the past 12 months after at least one line of prior therapy. Patients received nivolumab 240 mg every 2 weeks and ipilimumab 1mg/kg every 6 weeks for up to 2 years. Primary endpoint was objective response rate (ORR) by RECIST v1.1. Using a Simon’s 2-stage design, the study planned to accrue up to 56 patients. Based on published response rates to everolimus of 5%, we hypothesized that this regimen would be considered promising if the true ORR is > 15%. Results: Nine patients were enrolled prior to study closure due to funding, including 6 patients with NET of lung origin, 2 pancreatic, and 1 small bowel (Table). Median age was 71 years. All patients had distant metastatic disease at enrollment, with an average of 2 prior lines of therapy. Four of 9 patients achieved the primary endpoint of confirmed objective response, all of whom have ongoing response with a median duration of 15.4 months. Five of 9 patients, including all 4 responders, experienced immune-related toxicity requiring treatment modification or discontinuation. The trial did not accrue the target of 56 patients, however, objective response in 4 of 9 patients (ORR 44.4%, 90% CI: 16.9-74.9%) excluded the response rate target (15%). Conclusions: The impressive ORR of 44% with a median duration of response exceeding 15 months in this small clinical trial warrants further study of combination CTLA-4 and PD-1 inhibition in previously treated well-differentiated NET. Our ongoing immunologic and genomic correlative analysis in responders and non-responders will help inform future study of immunotherapy in this patient population in need of new systemic therapy approaches. Clinical trial information: NCT03420521. [Table: see text]

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