A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 480-480
Author(s):  
Carl Christoph Schimanski ◽  
Stefan Kasper ◽  
Susanna Hegewisch-Becker ◽  
Jan Schroeder ◽  
Friedrich Overkamp ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Cox Regression ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
High Recurrence Rate ◽  
Muc1 Expression ◽  
Double Blinded ◽  
Clinical Trial Information

480 Background: Hepatic metastasectomy is the only potential curative treatment option for stage IV colorectal cancer (CRC) limited to liver metastases (LM). After R0 resection of LM the high recurrence rate remains a major challenge. L-BLP25 is an antigen-specific cancer vaccine targeting mucin 1 (MUC1). The LICC trial aimed to improve survival outcome in mCRC patients (pts) after R0/R1 LM resection. Methods: This LICC trial, a binational, multicenter, double-blinded, placebo controlled phase II trial, included pts with stage IV LM limited CRC after resection of primary tumor and LM (R0/R1) within the last 8 weeks, ECOG 0/1 and adequate organ function. Pts were 2:1 randomized to receive L-BLP25 or placebo. L-BLP25 930 µg was administered as 8 weekly subcutaneous doses followed by 6 week maintenance intervals until recurrence or a maximum of 2 years. Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS), secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. Differences in RFS and OS were analyzed with exploratory log-rank tests on the intention-to-treat population. Results: Of 121 pts enrolled between Oct 2011 and Dec 2014, 79 pts received L-BLP25+CP, 42 placebo+NS. Baseline characteristics were well balanced. Median age was 60 years. Median RFS was 6.1 (90% CI: 5.8-8.8) vs. 11.4 months (90% CI: 5.0-20.3) and estimated 3-year OS rate 69.1% vs. 79.1% for L-BLP25 and placebo, respectively. Two-factorial Cox regression models showed no impact of MUC1 expression or treatment on RFS or OS. The most common L-BLP25-related grade 3/4 adverse events were diarrhea, anemia and back pain. There was one death in the L-BLP25 arm due to Merkel cell carcinoma assessed by the investigator as being potentially related to vaccination. Conclusions: The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513 . Clinical trial information: NCT01462513.

A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3537-3537
Author(s):  
Carl Christoph Schimanski ◽  
Stefan Kasper ◽  
Susanna Hegewisch-Becker ◽  
Jan Schroeder ◽  
Friedrich Overkamp ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Cox Regression ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
High Recurrence Rate ◽  
R0 Resection ◽  
Muc1 Expression ◽  
Mucin 1 ◽  
Double Blinded

3537 Background: Hepatic metastasectomy is the only potential curative treatment option for stage IV colorectal cancer (CRC) limited to liver metastases (LM). After R0 resection of LM the high recurrence rate remains a major challenge. L-BLP25 is an antigen-specific cancer vaccine targeting mucin 1 (MUC1). The LICC trial aimed to improve survival outcome in mCRC patients (pts) after R0/R1 LM resection. Methods: This LICC trial, a binational, multicenter, double-blinded, placebo controlled phase II trial, included pts with stage IV LM limited CRC after resection of primary tumor and LM (R0/R1) within the last 8 weeks, ECOG 0/1 and adequate organ function. Pts were 2:1 randomized to receive L-BLP25 or placebo. L-BLP25 930 µg was administered as 8 weekly subcutaneous doses followed by 6 week maintenance intervals until recurrence or a maximum of 2 years. Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS), secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. Differences in RFS and OS were analyzed with exploratory log-rank tests on the intention-to-treat population. Results: Of 121 pts enrolled between Oct 2011 and Dec 2014, 79 pts received L-BLP25+CP, 42 placebo+NS. Baseline characteristics were well balanced. Median age was 60 years. Median RFS was 6.1 (90% CI: 5.8-8.8) vs. 11.4 months (90% CI: 5.0-20.3) and estimated 3-year OS rate 69.1% vs. 79.1% for L-BLP25 and placebo, respectively. Two-factorial Cox regression models showed no impact of MUC1 expression or treatment on RFS or OS. The most common L-BLP25-related grade 3/4 adverse events were diarrhea, anemia and back pain. There was one death in the L-BLP25 arm due to Merkel cell carcinoma assessed by the investigator as being potentially related to vaccination. Conclusions: The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513.

Interim results of a randomized phase II study of PEGPH20 added to nab-paclitaxel/gemcitabine in patients with stage IV previously untreated pancreatic cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 439-439 ◽  
Author(s):  
Sunil R. Hingorani ◽  
William Proctor Harris ◽  
Tara Elisabeth Seery ◽  
Lei Zheng ◽  
Darren Sigal ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Randomized Study ◽  
Safety Data ◽  
Stage Iv ◽  
Phase Iii ◽  
Clinical Hold ◽  
Stage 1 ◽  
Clinical Trial Information

439 Background: Poor outcome in pancreatic cancer (PDA) is associated partly with stromal hyaluronan (HA) accumulation, which compromises chemotherapy perfusion. PEGPH20, PEGylated recombinant human hyaluronidase, potentiates chemotherapy by depleting HA in tumors. Methods: In an ongoing, phase II, open-label, randomized study of PEGPH20+nab-paclitaxel (Nab)+Gemcitabine (Gem) (PAG) vs Nab+Gem (AG) in previously untreated stage IV PDA, pts receive PEGPH20 3 µg/kg twice weekly (C1), then weekly (C2+) with standard AG dosing. HA status was tested retrospectively. After a temporary clinical hold (Apr-Jul 2014) for an imbalance in thromboembolic (TE) events (29% PAG vs 15% AG), the protocol was amended to exclude high-TE-risk pts and add enoxaparin (LMWH) prophylaxis. Endpoints are PFS and TE events (primary); PFS and ORR by HA level and OS (secondary). Efficacy and safety data through Dec 2014 are for pts enrolled up to clinical hold (Stage 1); TE data are through Sep 2015 (Stage 2). Results: 135 pts were treated (74 PAG, 61 AG). PFS results are shown below (median follow-up 7 mo). In HA-high pts receiving PAG vs AG, ORR was 52% (1 CR) vs 24% (P=.038); ORR was 37% vs 38% in HA-low pts. OS was 12 mo vs 9 mo (HR=0.62) despite 12/23 PAG pts discontinuing PEGPH20 at clinical hold. Common ADRs (PAG vs AG) included peripheral edema (58% vs 31%), muscle spasms (55% vs 1.6%), and neutropenia (32% vs 18%). TE events were: Stage 1 42% vs 25% (no LMWH); Stage 2 (with LMWH; 40 mg/d or 40 mg/d increased to 1 mg/kg/d) 28% vs 29%; (1 mg/kg/d) 5% vs 6%; overall (40 mg/d or 1 mg/kg/d) 13% each arm (to be updated). Conclusions: Pts with HA-high tumors receiving PAG, vs AG, showed significant improvements in PFS and ORR and a trend toward improved OS. PAG was well tolerated, with TE events reduced with LMWH prophylaxis. A global phase III trial of PAG will initiate Q1 2016. Clinical Trial Information: NCT01839487. Clinical trial information: NCT01839487. [Table: see text]

Efficacy and safety results from neopembrov study, a randomized phase II trial of neoadjuvant chemotherapy (CT) with or without pembrolizumab (P) followed by interval debulking surgery and standard systemic therapy ± P for advanced high-grade serous carcinoma (HGSC): A GINECO study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5500-5500
Author(s):  
Isabelle Laure Ray-Coquard ◽  
Aude Marie Savoye ◽  
Marie-ange Mouret-Reynier ◽  
Sylvie Chabaud ◽  
Olfa Derbel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Figo Stage ◽  
Complete Resection ◽  
Serous Carcinoma ◽  
Debulking Surgery ◽  
Randomized Phase Ii ◽  
Interval Debulking Surgery ◽  
Clinical Trial Information

5500 Background: To investigate whether adding Pembrolizumab (P) to neoadjuvant carboplatin-paclitaxel chemotherapy (CP) may increase the optimal debulking rate, assessed by Complete Resection Rate (CRR) after Interval Debulking Surgery (IDS) in patients (pts) with initially unresectable International Federation of Gynecology and Obstetrics (FIGO) stage IIIC/IV ovarian, tubal or peritoneal HGSC. Methods: Multicenter, open-label, non-comparative randomized phase II trial. Pts were randomized (2:1) to receive 4 cycles of CP ± P before IDS. After IDS, all patients received post-operative chemotherapy (2 to 4 cycles) and optional bevacizumab for 15 months in total ± P as maintenance therapy for up to 2 years. Randomization was stratified on center, FIGO stage, Bev planned after IDS and disease volume (<5cm/>5cm). Primary endpoint was the centrally reviewed CRR at IDS. 60 pts were planned in the CP+P arm (A'Hern's single-stage design P0=50%, P1=70%). Safety (particularly due to P addition), surgical morbidity, ORR, PFS and OS were secondary endpoints. Results: 91 pts were randomized from 02/18 to 04/19 with a median Peritoneal Cancer Index at 24 (range 7-39). 80 pts (88%) received Bev in combination with CP followed by bev ± P in maintenance. In the CP+P group (n=61), 58 (95%) pts had IDS and 78% achieved complete resection. The CRR in this group was 74%, statistically superior to the pre-defined hypothesis. In the CP group, CRR was 70% (29/30 pts underwent IDS). Complete resection after strictly 4 cycles of CP±P was obtained for 41 pts (71%) and 17 (58%) pts in CP+P and CP group, respectively (sensitivity analysis). For CP+P group, numerically higher ORRs were observed before IDS compared to CP group (76% vs 61%). Grade ≥3 adverse events (AE) occurred in 75% of the CP+P group and 67% in the CP group: mainly blood and lymphatic, gastrointestinal and vascular disorders. Postoperative AE (mainly infectious, vascular and gastrointestinal) occurred in 20% and 13% of the pts in CP+P and CP arm, respectively. No difference in the number of fatal events between the two arms: 2 in the experimental arm vs 1 in the control arm. Progression free survival rate at 18 months was 61% (95CI% [47-73]) and 57% (95CI% [37-72]) in CP+P and CP arm, respectively. Conclusions: P may be safely added to preoperative treatment in pts deemed non-optimally resectable. The primary objective was met with an improved CRR on CP+P arm. The CRR in the control group was higher than expected. Survival data and translational research including PDL1 status are ongoing to better define P as treatment option in this setting. Clinical trial information: 2016-004-163-39. Clinical trial information: NCT03275506.

Capecitabine maintenance therapy after adjuvant chemotherapy of FOLFOX (or XELOX) in patients with stage IIIC or R0 resected stage IV colorectal cancer (CAMCO study).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS781-TPS781
Author(s):  
Jiayu Ling ◽  
Wenjing Wang ◽  
Shanshan Li ◽  
Yue Cai ◽  
Huabin Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Maintenance Therapy ◽  
Stage Iv ◽  
Stage Iiic ◽  
Resected Stage ◽  
Clinical Trial Information

TPS781 Background: Surgical resection and adjuvant therapy has become the main treatment for resectable colorectal cancer (CRC). Treatment with current strategies, however, recurrent rate is high for stage IIIc or R0 resected stage IV CRC (high risk-CRC). For some other maglinancies with high risk of recurrence, such as gastric cancer or high-risk gastrointestinal stromal tumor, longer period of postoperative chemotherapy was applied. The effectiveness of maintenance therapy following standard adjuvant chemotherapy in high risk-CRC has not been verified in clinical trial. Capecitabine is is an orally-administered chemotherapeutic agent used in the treatment of CRC, either as neoadjuvant therapy with radiation, adjuvant therapy or for metastatic cases. This study is exploring the efficacy and safety of strategy of surgical resection and adjuvant chemotherapy followed by maintenance capecitabine for stage IIIC or R0 resected stage IV CRC. Methods: The study was designed as an open-label phase II trial with 200 patients assigned to two thearapy group: experimental arm A (Adjuvant chemotherapy with mFOLFOX6 or XELOX for more than four months + oral capecitabine 1000mg/m2 twice daily days1-14 every 3 weeks for 12 months maintenance) or standard arm B (Adjuvant chemotherapy with mFOLFOX6 or XELOX for more than four months + observation). Eligibility included patients of 18-80 years of age, diagnosis of adenocarcinoma of the colon or rectum, received curative resection when diagnosed, with postoperative stage of IIIC OR IV(R0 resected), PS 0-1 and adequate organ function. Doses were modified for hand-foot syndrome, diarrhea and other grade 3 toxicities. The primary aim is to evaluate the 3 year disease free survival of the patients. Secondary aims inclued overall survival, safety, quality of life and an assessment of predictive molecular markers of maintenance strategy. After completion of adjuvant treatment, patients are followed every 3 months for 2 years, and then every 6 months for 3rd-5th years. This study is now open to accrual in The Sixth Affiliated Hospital of Sun Yat-sen University. Clinical trial information: NCT01880658. Clinical trial information: NCT01880658.

Consensus molecular subtype (CMS) as a novel integral biomarker in colorectal cancer: A phase II trial of bintrafusp alfa in CMS4 metastatic CRC.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4084-4084 ◽  
Author(s):  
Amir Mehrvarz Sarshekeh ◽  
Michael Lam ◽  
Isabel R. Zorrilla ◽  
Emma Brey Holliday ◽  
Prajnan Das ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
De Novo ◽  
Phase Ii Trial ◽  
Molecular Subtype ◽  
Median Number ◽  
Primary Objective ◽  
Primary Tumors ◽  
Consensus Molecular Subtype

4084 Background: Consensus Molecular Subtype 4 (CMS4) colorectal cancer (CRC) features increased TGFβ signaling, which may account for de novo resistance to immunotherapy for patients (pts) with microsatellite stable mCRC. To date, no prior trial has incorporated CMS status as an integral biomarker. Bintrafusp alfa (M7824) is a dual PD-L1 antibody/TGFβ trap with acceptable safety. Methods: Primary tumors from pts with metastatic CRC underwent CMS testing in a CLIA setting. In this Simon two-stage phase II trial (Ho: p < .05; Ha: p≥.25) for CMS4 mCRC, pts received bintrafusp alfa 1200mg IV every 14 days. RT (8Gy/day x 3 days) to a single metastatic lesion with abscopal intent was administered between doses 2 and 3. The primary objective was to estimate response rate (RR) per iRECIST. Correlative studies including RNA sequencing were performed on pre- and on-treatment biopsies. Results: 53 of 137 tested pts (39%) between June 2018-December 2019 had CMS4 mCRC. 13 of 15 treated pts received the agent with RT. All pts were evaluable for toxicity, and 13 for response. Median number of doses was 3 (IQR, 2-4). There was one grade 3 immune-related adverse event (colitis) requiring study discontinuation. There were 2 pts with stable disease and 11 with progressive disease as best response (RR 0%, 95% CI 0-22%). Enrollment was stopped after first stage for futility. Median PFS and OS were 1.6 months and 5.0 months, respectively. In paired samples, treatment with bintrafusp alfa resulted in an increase in the expression of IFNγ signature in nonirradiated metastatic lesions ( p< .001, q< .001). Updated results will be presented. Conclusions: This is the first reported clinical trial to utilize CMS status as an integral biomarker for pts with metastatic CRC and capitalizes on treating CRC subpopulations with targeted agents based upon validated RNA-based signatures. Although the efficacy for bintrafusp alfa and RT is low, changes in IFNγ signature provides a potential signal for refining therapeutic strategies based upon TGFβ enrichment in pts with mCRC. Clinical trial information: NCT03436563 .

NIVACOR: Phase II study of nivolumab in combination with FOLFOXIRI/bevacizumab in first-line chemotherapy for advanced colorectal cancer RASm/BRAFm patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4118-TPS4118
Author(s):  
Angela Damato ◽  
Francesco Iachetta ◽  
Nicola Normanno ◽  
Francesca Bergamo ◽  
Evaristo Maiello ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
First Line ◽  
Flat Dose ◽  
Braf Mutant ◽  
Clinical Trial Information

TPS4118 Background: FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab has been shown to be one of the therapeutic regimens in first line with the highest activity profile in patients (pts) with metastatic colorectal cancer (mCRC) unselected for biomolecular alterations. Tumors co-opt the PD-1/PD-L1 signaling pathway as one key mechanism to evade immune destruction. Anti-PD-1 monoclonal antibodies are FDA approved only for DNA mismatch repair deficient/microsatellite instability-high (MMRd/MSI-H), which are only about 5% among all mCRC. Nowadays, there are no data demonstrating anti-PD1 activity in stable and proficient (MMRp/MSS) disease. Another critical therapeutic target is the Vascular Endothelial Growth Factor A (VEGF-A), which acts on endothelial cells to stimulate angiogenesis; his inhibition with bevacizumab increase immune cell infiltration, giving a strong rationale for combining VEGF targeted agents with immune checkpoint inhibitors. Based on evidence, we explore the combination of triplet chemotherapy (FOLFOXIRI) with bevacizumab and nivolumab in pts with mCRC all- RAS/BRAF mutant regardless of microsatellite status. Methods: This is a prospective, open-label, multicentric phase II trial where pts with mCRC RAS/BRAF mutant in first line will receive nivolumab in combination with FOLFOXIRI/Bevacizumab every 2 weeks for 8 cycles followed by maintenance with bevacizumab plus nivolumab every 2 weeks. Bevacizumab will be administered intravenously at dose of 5 mg/kg every 2 weeks and nivolumab intravenously as a flat dose of 240 mg every 2 weeks. The primary endpoint is the overall response rate (ORR) and our hypothesis is that the treatment is able to improve the ORR from 66% to 80%. Secondary endpoints include overall survival, safety, time to progression, duration of response. Collateral translational studies evaluate the tumor mutational burden, and genetic alterations by circulating free DNA (cfDNA) obtained from plasma samples. The trial is open to enrollment, 4 of planned 70 pts have been enrolled. Clinical trial information: EudraCT Number: 2018-002893-38. Clinical trial information: NCT04072198 .

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