A global phase II trial-in-progress with bavituximab plus pembrolizumab in patients with advanced gastric or gastroesophageal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS459-TPS459
Author(s):  
Jeeyun Lee ◽  
Kerry Culm-Merdek ◽  
Jessicca Martin Rege ◽  
Andrew William Pippas ◽  
Johanna C. Bendell ◽  
...  
Keyword(s):  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Phase Iii ◽  
Open Label ◽  
Treatment Naïve ◽  
Third Line ◽  
Expansion Cohort ◽  
Biomarker Signature

TPS459 Background: The majority of gastric cancer (GC) patients fail to derive sufficient benefit from currently available therapies. Pembrolizumab received accelerated approval in 2017 as a third-line therapy in PD-L1 positive GC patients with an ORR of 13.3%. Further studies in second- and third-line GC patients showed comparable outcomes when pembrolizumab was combined with chemotherapy. Bavituximab, an investigational, chimeric monoclonal antibody designed to inhibit the immunosuppressive effects of phosphatidylserine (PS), is being evaluated in combination with pembrolizumab in patients with advanced gastric and gastroesophageal junction (GEJ) cancer. Bavituximab binds in a high-affinity complex with β2-glycoprotein and PS to reverse immunological non-responsiveness and activate multiple immune cell receptors, including TIMS and TAMS. Data from the Phase III Sunrise second-line lung cancer study indicated that patients who progressed on study treatment with bavituximab plus docetaxel and continued with a checkpoint inhibitor showed significantly improved overall survival. Cumulative data suggest that bavituximab may potentiate pembrolizumab-mediated checkpoint inhibition, potentially increasing overall clinical benefit. Methods: This phase 2, multicenter, open-label, single-arm global study is designed to assess the safety, tolerability and efficacy of the bavituximab-pembrolizumab combination in advanced gastric or GEJ adenocarcinoma patients, regardless of PD-L1 status, who have progressed on or after at least one prior standard therapy. Patients must be treatment naïve for checkpoint inhibitors. The study, started in August 2019, consists of an initial 3+3 de-escalation safety cohort to confirm the expansion cohort dose. A total of 80 patients will be enrolled. Primary endpoints will assess antitumor activity of the treatment combination on objective response rate using RECIST1.1, safety and tolerability. Secondary endpoints will evaluate antitumor characteristics, pharmacokinetics, and immunogenicity. Exploratory objectives include the evaluation of a novel biomarker signature panel and its relationship to efficacy outcomes.

Tailored immunotherapy approach with nivolumab in advanced transitional cell carcinoma (TITAN-TCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 446-446
Author(s):  
Marc-Oliver Grimm ◽  
Bernd Schmitz-Dräger ◽  
Uwe Zimmermann ◽  
Barbara Grün ◽  
Gustavo Bruno Baretton ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Transitional Cell ◽  
Added Value ◽  
Phase Iii ◽  
First Line ◽  
Third Line

446 Background: Several PD-1 immune-checkpoint inhibitors including Nivolumab (Nivo) are approved in urothelial cancer. Recently, in the front line setting, improved activity of combined PD-L1 and CTLA4 immune-checkpoint inhibition has been reported and a phase III trial with Nivolumab + Ipilimumab (Nivo+Ipi) is ongoing. Here we report a response-based tailored approach starting treatment with Nivo monotherapy using Nivo+Ipi as immunotherapeutic “boost”. Methods: Between July 2017 and April 2019 86 patients were enrolled and treated according to protocol version 3 (cohort 1). Patients started with Nivo 240 mg Q2W induction. After 4 dosings and tumor assessment at week 8 (i) responders (PR/CR) to Nivo monotherapy continued with maintenance while (ii) patients with stable (SD) or progressive disease (PD) received 2 cycles Nivo3+Ipi1 followed by another 2 cycles Nivo1+Ipi3 if not responding. Median follow-up is 8.7 months. The primary endpoint is confirmed investigator-assessed objective response rate (ORR) per RECIST1.1. Secondary endpoints include activity of Nivo monotherapy at week 8, remission rate with Nivo+Ipi “boosts”, safety, overall survival and quality of life. Results: Of the patients 42, 39 and 5 were first, second and third line, respectively. Median age was 67 years (range 45-84), 61 patients (71 %) were male and 25 female. ORR with Nivo monotherapy at first assessment (week 8) was 29 % and 23 % in first and second/third line, respectively. Of the patients 41 received Nivo+Ipi “boosts” after week 8 while 12 received later “boosts”. Best overall response (BOR) rate with Nivo induction ± Nivo+Ipi “boosts” was 48 % and 27 % in first and second/third line, respectively. In first line 7/17 (41 %) patients receiving Nivo+Ipi after week 8 had an improved response compared to 2/24 (8.3 %) in second/third line. Of the patients who continued with Nivo maintenance after week 8 and received later “boosts” 2/12 (17 %) had a PR and 2/12 (17 %) improved to SD. Treatment-related AEs will be presented. Conclusions: TITAN–TCC explores a response-driven use of Nivo+Ipi as an immunotherapeutic “boost”. In first line, this significantly improved ORR compared to the expected response rate of Nivo monotherapy, providing further evidence to the added value of Ipi in combination with Nivo. Further follow-up is ongoing to characterize duration and depth of response. Clinical trial information: NCT03219775 . Research Sponsor: Bristol-Myers Squibb[Table: see text]

IMPALA, a randomized phase III study in patients with metastatic colorectal carcinoma: Immunomodulatory maintenance therapy with TLR-9 agonist MGN1703.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. TPS791-TPS791 ◽  
Author(s):  
David Cunningham ◽  
Alfredo Zurlo ◽  
Ramon Salazar ◽  
Michel Ducreux ◽  
Tom Samuel Waddell ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Immune Cell ◽  
Cox Regression ◽  
Objective Response ◽  
Phase Iii ◽  
Induction Treatment ◽  
Self Administration ◽  
Open Label ◽  
Response To Chemotherapy ◽  
To Receive

TPS791 Background: The potent TLR-9 agonist MGN1703, a synthetic DNA-based immunomodulator, was compared to placebo in metastatic colorectal cancer (mCRC) patients with disease control after standard induction chemotherapy +/- bevacizumab in the phase II IMPACT trial and showed a superior effect with a hazard ratio for the primary endpoint PFS on maintenance of 0.55 (p=0.041) by local investigator assessment and 0.56 (p=0.070) by independent radiological review. In the MGN1703 arm 3 objective responses were observed, two of them appearing as late as 9 months after the start of treatment. At time of study closure 4 MGN1703 patients were still without progressive disease and continued treatment by self-administration in a compassionate use setting. Exploratory Cox regression and ROC analyses suggested a potential predictive role at baseline for normal CEA, objective response to prior chemotherapy and presence of activated NKT-cells. Methods: The pivotal IMPALA study has been designed to confirm these data and started to enroll patients with smaller tumor burden after a good response to chemotherapy, as best candidates to receive a maintenance treatment with immunotherapy. IMPALA is a randomized, international, multicenter, open-label phase III trial that will include 540 patients from 120 centers with the collaboration of the AIO, TTD, and GERCOR cooperative groups and is currently recruiting patients. In this study mCRC patients with an objective tumor response following any first line induction therapy will be randomized to MGN1703 monotherapy maintenance or local standard of care. At time of relapse, patients will reintroduce the induction treatment whenever feasible, with those in the experimental arm continuing to receive MGN1703 in the weeks without chemotherapy. Patients will also be stratified by CEA level and activated NKT at baseline. The primary endpoint of the study will be overall survival. Secondary endpoints include PFS, response rates, safety, and QoL in selected centers. All patients will be evaluated for cytokines and chemokines in serum and the activation status of various immune cell populations. Clinical trial information: NCT02077868.

Initial safety run-in findings with bavituximab plus pembrolizumab in patients with advanced gastric or gastroesophageal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16537-e16537
Author(s):  
Ian Chau ◽  
Haeseong Park ◽  
Jeeyun Lee ◽  
Jessicca Martin Rege ◽  
Kerry Culm-Merdek ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Cell ◽  
Gastroesophageal Junction ◽  
Safety Data ◽  
Chylous Ascites ◽  
Phase Iii ◽  
Open Label ◽  
Agent Based ◽  
Starting Dose ◽  
Post Hoc

e16537 Background: Bavituximab, an investigational, chimeric monoclonal antibody designed to inhibit the immunosuppressive effects of phosphatidylserine (PS), is being evaluated in combination with pembrolizumab in patients with advanced gastric and gastroesophageal junction (GEJ) cancer. Bavituximab binds in a high-affinity complex with β2-glycoprotein and PS to reverse immunological non-responsiveness and activate multiple immune cell receptors. Post-hoc data from the Phase III Sunrise second-line lung cancer study indicated that patients who progressed on study treatment with bavituximab plus docetaxel and continued with a checkpoint inhibitor showed significantly improved overall survival. Cumulative data suggest that bavituximab may potentiate pembrolizumab-mediated checkpoint inhibition, potentially increasing overall clinical benefit. ONCG100 is a phase 2, multicenter, open-label, single-arm global study designed to assess the safety, tolerability and efficacy of bavituximab and pembrolizumab when administered in combination to advanced gastric or GEJ adenocarcinoma patients, regardless of PD-L1 status, who have progressed on or after at least one prior standard therapy (NCT04099641). Methods: The safety run-in phase of the trial evaluated the safety and tolerability of de-escalating doses of bavituximab when administered in combination with the approved dose and schedule of pembrolizumab (200mg, Q3W). Adverse events were evaluated by CTCAE v5.0. Results: Three patients enrolled and completed the safety-run in phase of the study where bavituximab was administered at the starting dose of 3 mg/kg QW in combination with pembrolizumab. There were no dose-limiting toxicities observed during the 21-day monitoring period. A total of 4 treatment emergent adverse events were observed; 2 of which were reported as related to treatment with bavituximab (arthralgia and fatigue, both grade 1). There was one treatment-unrelated SAE reported (chylous ascites, grade 2), which resolved allowing the patient to continue treatment. Conclusions: The 3 mg/kg dose of bavituximab was readily combined during the safety run-in phase of the study with the approved dose of pembrolizumab. The AE profiles for this combination were manageable and expected given the known profiles of each agent. Based upon these findings, the recommended dose for expansion for the combination was declared and the expansion phase of the study opened. Updated safety data from the study will be presented. Clinical trial information: NCT04099641 .

CA045-001: A phase III, randomized, open label study of bempegaldesleukin (NKTR-214) plus nivolumab (NIVO) versus NIVO monotherapy in patients (pts) with previously untreated, unresectable or metastatic melanoma (MEL).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9601-TPS9601 ◽  
Author(s):  
Nikhil I. Khushalani ◽  
Adi Diab ◽  
Paolo Antonio Ascierto ◽  
James M.G. Larkin ◽  
Shahneen Kaur Sandhu ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Phase 1 ◽  
Objective Response ◽  
Development Program ◽  
Life Assessment ◽  
Phase Iii ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Study ◽  
Label Study

TPS9601 Background: Standard of care for pts with previously untreated, unresectable or metastatic MEL includes checkpoint inhibitors. Bempegaldesleukin is a CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 βγ receptor to activate and proliferate effector CD8+ T and NK cells over T-regulatory cells in the tumor (Hurwitz ME et al. ASCO GU 2017). In the dose-expansion phase of the phase 1/2 PIVOT-02 trial, bempegaldesleukin + NIVO was well tolerated at the recommended phase 2 dose (RP2D; bempegaldesleukin 0.006 mg/kg IV Q3W + NIVO 360 mg IV Q3W), and previously untreated pts with MEL receiving the RP2D achieved an objective response rate (ORR) of 20/38 (53%) and a complete response of 9/38 (24%) by independent radiology review (Diab A et al. SITC 2018). Presented is the design of the first phase 3 trial in the bempegaldesleukin + NIVO development program in pts with previously untreated, unresectable or metastatic MEL. Methods: This phase 3, randomized, open-label study aims to evaluate the effectiveness, safety, and tolerability of bempegaldesleukin + NIVO (NCT03635983). Eligible pts are ≥12 y with histologically confirmed stage III (unresectable) or stage IV MEL and ECOG PS ≤1 or Lansky PS ≥80% (minors 12-17 y). Pts are ineligible if they have active brain or leptomeningeal metastases, uveal MEL, or a recurrence within 6 mo of completing adjuvant treatment with any approved agent. Pts will be stratified by PD-L1 status (measured using PD-L1 IHC 28-8 pharmDx), BRAF mutation status, and lactate dehydrogenase level, and will be randomized to receive bempegaldesleukin 0.006 mg/kg IV Q3W + NIVO 360 mg IV Q3W or NIVO 360 mg IV Q3W up to 24 mo, or until progression or unacceptable toxicity (N ~ 764). Primary endpoints are ORR and progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints include ORR and PFS by investigator, ORR and PFS by BICR in biomarker population, OS in biomarker population, and safety. Additional endpoints include pharmacokinetics and quality-of-life assessment. Clinical trial information: NCT03635983.

Margetuximab (M) combined with anti-PD-1 (retifanlimab) or anti-PD-1/LAG-3 (tebotelimab) +/- chemotherapy (CTX) in first-line therapy of advanced/metastatic HER2+ gastroesophageal junction (GEJ) or gastric cancer (GC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS264-TPS264
Author(s):  
Daniel V.T. Catenacci ◽  
Minori Koshiji Rosales ◽  
Hyun Cheol Chung ◽  
Harry H. Yoon ◽  
Lin Shen ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Checkpoint Inhibitors ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Open Label ◽  
Double Positive ◽  
Line Therapy

TPS264 Background: Trastuzumab (T), a monoclonal antibody (mAb) targeting HER2, is standard of care 1st-line therapy for advanced HER2+ GEJ/GC patients. M, an investigational Fc-engineered anti-HER2 mAb, targets the same HER2 epitope but with higher affinity for both 158V (high binding) and 158F (low binding) alleles of activating Fc receptor CD16A. Data suggest margetuximab coordinately enhances both innate and adaptive immunity, including antigen-specific T-cell responses to HER2. PD-1 and LAG-3 are T-cell checkpoint molecules that suppress T-cell function. Retifanlimab (also known as MGA012 or INCMGA00012) is a humanized, hinge-stabilized, IgG4 Κ anti-PD-1 mAb blocking binding of PD-L1 or PD-L2 to PD-1. Tebotelimab (also known as MGD013) is a humanized Fc-bearing bispecific tetravalent DART® protein that binds to both PD-1 and LAG-3, inhibiting their respective ligand binding. We previously reported that a CTX-free regimen of M+PD-1 blockade was well tolerated in GEJ/GC patients, and induced a 44% objective response rate (ORR) in a double-positive biomarker population. This was 2- to 3-fold greater than in historical controls with checkpoint inhibitors alone. This registration-directed trial assesses efficacy, safety, and tolerability of M+checkpoint inhibition ± CTX in metastatic/locally advanced, treatment-naïve, HER2+ GEJ/GC patients. Methods: This is a 2-cohort, adaptive open-label phase 2/3 study (NCT04082364). The first single arm, CTX-free cohort A, evaluates M+retifanlimab in HER2+ (immunohistochemistry [IHC] 3+) and PD-L1+ (excluding microsatellite instability high) patients. After 40 patients are evaluated for response/safety, additional patients will be enrolled if the threshold for continuation is met. In randomized cohort B, HER2+ (IHC 3+ or 2+/fluorescent in situ hybridization+) patients are enrolled irrespective of PD-L1 status. Part 1 of cohort B randomizes patients to 1 of 4 arms (50 patients each): control arm (T+CTX) or 1 of 3 experimental arms (M+CTX; M+CTX+retifanlimab; M+CTX+tebotelimab). CTX is investigator’s choice XELOX or mFOLFOX-6. Part 2 of cohort B consists of control (T+CTX) vs 1 experimental arm (M+CTX) + either retifanlimab or tebotelimab, depending on results from part 1; with 250 patients each. The primary efficacy endpoint for cohort A (both parts) is ORR per RECIST 1.1; for cohort B part 2 it is overall survival. Clinical trial information: NCT04082364.

Survival of patients (pts) with metastatic melanoma treated with the anti-CTLA4 monoclonal antibody (mAb) CP-675,206 in a phase I/II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8524-8524 ◽  
Author(s):  
J. Gomez-Navarro ◽  
S. Antonia ◽  
J. Sosman ◽  
J. M. Kirkwood ◽  
B. Redman ◽  
...  
Keyword(s):  
Phase I ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Phase Ii ◽  
Survival Data ◽  
Phase I Study ◽  
Objective Response ◽  
Phase Iii ◽  
Open Label ◽  
Expansion Cohort

8524 Background: The fully human anti-CTLA4 mAb CP-675,206 has demonstrated clinical activity in pts with metastatic melanoma. Prolonged survival was observed in a prior single-dose phase I study, even in pts who did not achieve objective tumor responses. Methods: A multidose phase I/II trial was conducted in pts (N = 119) with histologically confirmed stage IIIc (unresectable) or stage IV recurrent metastatic melanoma and ECOG PS = 1. The study consisted of a phase I, open-label, multidose study (3, 6, and 10 mg/kg) and a phase I expansion cohort for HLA-A2.1+ pts (10 mg/kg monthly [Q1M]), followed by a phase II open-label study of 2 dosing regimens: 10 mg/kg Q1M and 15 mg/kg every 3 months (Q3M). The primary endpoint was safety in phase I, immune monitoring in the expansion cohort, and response in phase II. Survival was analyzed as a secondary endpoint. Results: In the phase I study, Kaplan-Meier estimates of median overall survival were 17.6 months for all dose groups combined (n = 28). In the phase II study, median survival was 10.3 months in the 10 mg/kg arm and 11.0 months in the 15 mg/kg arm. Survival outcomes were favorable, compared with historical median survival of 7 months, independent of whether pts achieved an objective response. Updated survival data will be presented. Conclusions: Patients participating in a multiple dose study of CP-675,206 showed a survival time that was greater than expected on historic controls. These observations support the endpoints of an ongoing randomized phase III study in melanoma to further evaluate survival in the frontline setting. [Table: see text] [Table: see text]

Updated results of a phase 1 study combining the matrix metalloproteinase 9 inhibitor GS-5745 and mFOLFOX6 in patients with advanced gastric/gastroesophageal junction cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 108-108 ◽  
Author(s):  
Manish A. Shah ◽  
Alexander Starodub ◽  
Jordan Berlin ◽  
Carrie Baker Brachmann ◽  
Xi Huang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Matrix Metalloproteinase 9 ◽  
Dose Finding ◽  
Phase Iii ◽  
Matrix Remodeling ◽  
Treatment Naïve ◽  
Metalloproteinase 9

108 Background: GS-5745 is a monoclonal antibody inhibitor of matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. We present updated data from a phase I study of patients (pts) with advanced gastric/gastroesophageal adenocarcinoma (GC) treated with GS-5745 and mFOLFOX6 (NCT01803282). Methods: Following a monotherapy dose finding stage, pts with Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced or metastatic GC received mFOLFOX6 and GS-5745 (800 mg IV) every 2 weeks. Treatment continued until disease progression, unacceptable toxicity or withdrawal of consent. Response was assessed every 8 weeks per RECIST version 1.1 criteria. Results: As of April 2016, 40 pts were enrolled in the expanded cohort (12 continue to receive GS-5745). The most frequently observed adverse events (AEs) of any grade include nausea (62.5%), fatigue (60%), diarrhea (45%), peripheral neuropathy (45%) and neutropenia (37.5%). Grade ≥ 3 AEs observed in ≥ 10% of pts include neutropenia (20%) and nausea and neutrophil count decreased (10% each). Among 29 treatment naïve pts, median progression free survival (PFS) is 12 (90% confidence interval (CI) 5.5-18) months (mos), median duration of response (DOR) 10.6 mos and objective response rate (ORR) of 55.2%. For all pts (n=40), PFS is 7.8 (90% CI 5-13.9) mos, median DOR 10.1 mos and ORR of 50%. Median baseline circulating MMP9 was 44.7 (range 16.8-1395.3) ng/mL and all 34 patients with post-baseline samples had undetectable MMP9 levels within 8 weeks. Conclusions: The combination of GS-5745 with mFOLFOX6 is well tolerated and demonstrates activity, particularly in treatment naïve pts. Reduction in circulating MMP9 level after treatment with GS-5745 suggests specific target engagement. A phase III registration study of mFOLFOX6 +/- GS-5745 in treatment naïve metastatic GC pts is underway. Clinical trial information: NCT01803282.

A phase 2 trial of CRS-207 and pembrolizumab in adults with recurrence of metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinomas.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS200-TPS200
Author(s):  
Ronan Joseph Kelly ◽  
Thomas Adam Abrams ◽  
Daniel V.T. Catenacci ◽  
Zev A. Wainberg ◽  
Bruce Shih-Li Lin ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Clinical Activity ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Phase 2 ◽  
Open Label ◽  
Mesothelin Expression

TPS200 Background: CRS-207 is a live, attenuated, double-deleted Listeria monocytogenes (LADD) strain with a mesothelin expression cassette inserted. CRS-207 has a well-established, manageable toxicity profile and can elicit mesothelin-specific cell-mediated immunity. Clinical activity of CRS-207 has been shown in a separate Phase 1 trial of mesothelioma. In gastroesophageal (GE) cancers, mesothelin expression is estimated between 30% – 50% and has been correlated with poor prognosis. Preclinical models suggest the combination of LADD-based immunotherapeutics and a PD1 inhibitor may induce more sustained anti-tumor responses than either LADD or PD1 inhibitor monotherapy. GE cancers are responsive to PD1 inhibitors in a subset of patients; this trial proposes to evaluate the efficacy of CRS-207 combined with pembrolizumab in patients with relapsed GE cancer, and to correlate clinical activity with mesothelin expression level. Methods: This Phase 2, open-label, single-arm, multicenter clinical study (NCT 03122548) will enroll approximately 79 subjects at 20 sites. Adults with histologically-confirmed, advanced gastric, GEJ, or esophageal adenocarcinomas are eligible. Subjects must have received 1 or 2 prior treatment regimens, which must have included a platinum and a fluoropyrimidine. Subjects must have disease progression with measurable tumors. A pre-treatment biopsy of either the primary tumor or metastatic site is required prior to dosing. Subjects with prior exposure to checkpoint inhibitors or other immunotherapies are excluded. From cycle 1 to 4 during the treatment and evaluation period, pembrolizumab (IV 200 mg) and CRS-207 (IV 1 x 109 CFU) are both administered in 3-week cycles. Afterward, pembrolizumab will be administered once every 3 weeks; CRS-207 will be given once every 6 weeks. CT scans will be performed every 6 weeks to monitor disease status. The primary endpoint is objective response rate defined by RECIST 1.1. Clinical trial information: NCT03122548.

ATALANTE-1 randomized phase III trial, OSE 2101 versus standard treatment as second- or third-line in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9121-TPS9121 ◽  
Author(s):  
Enriqueta Felip ◽  
Giuseppe Giaccone ◽  
Rafal Dziadziuszko ◽  
Fabrice Denis ◽  
Teresa Moran ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Phase Iii ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Third Line ◽  
Nsclc Patients

TPS9121 Background: New treatment strategies are needed for advanced NSCLC patients who progress on treatment with immune checkpoint inhibitors (ICI). Tedopi (OSE2101) is a neoepitope vaccine restricted to HLA-A2 positive patients (45%) targeting five tumor-associated antigens frequently expressed in lung cancer cells, ACE, HER2, MAGE2, MAGE3 and P53. Previously, in a phase II trial (Barve et al. JCO 2008), Tedopi showed a median overall survival (OS) of 17.3 months with a manageable safety profile in advanced NSCLC patients. ATALANTE-1 (NCT02654587) is a randomized, open-label, phase 3 study comparing the efficacy and safety of TEDOPI with standard of care (SoC) treatment in HLA-A2 positive patients with advanced NSCLC, as second- or third-line therapy. Methods: Patients with advanced NSCLC without EGFR-sensitizing mutations or ALK rearrangements; progressive disease to platinum-based chemotherapy (ChT) with sequential or concurrent ICI; HLA-A2 positivity (blood test); ECOG PS 0-1; with treated and asymptomatic brain metastases,, are randomized 2:1 to receive 5mg Tedopi subcutaneously Q3W for 6 cycles, then Q8W for the reminder of the year and finally Q12W, or SoC treatment with: docetaxel 75 mg/m2 Q3W or pemetrexed 500 mg/m2 Q3W (in non-squamous and pemetrexed-naïve patients). Treatment continues until progression, intolerable toxicity or consent withdrawal, in both arms. Patients are stratified by histology, best response to first line, and line rank of ICI. Tumor assessment is performed every 6 weeks (RECIST 1.1). Primary endpoint is OS. Secondary end points are PFS, ORR, DCR, and duration of response, quality of life and safety. This is a superiority study with a hazard ratio of 0.7, two-sided alpha 5% and power 80%, after 278 events are observed. An independent analysis (1year OS rate) is planned in the first 84 patients treated with Tedopi. Last trial review by the DMC in June 18 suggested that the trial continues as planned. Translational research will be performed evaluating pharmacodynamic markers of efficacy such as immunogenicity response against Tedopi vaccine neoantigens, as well as parameters in liquid and tissue biopsies. End January 19, 87 patients (51 Tedopi, 36 Soc) have been enrolled. Clinical trial information: NCT02654587.

Margetuximab (M) combined with anti-PD-1 (MGA012) or anti-PD-1/LAG-3 (MGD013) +/- chemotherapy (CTX) in first-line therapy of advanced/metastatic HER2+ gastroesophageal junction (GEJ) or gastric cancer (GC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS468-TPS468
Author(s):  
Daniel V.T. Catenacci ◽  
Minori Koshiji Rosales ◽  
Jon M. Wigginton ◽  
Hyun Cheol Chung ◽  
Harry H. Yoon ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Checkpoint Inhibitors ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Open Label ◽  
First Line Therapy ◽  
Line Therapy

TPS468 Background: Trastuzumab (T), a monoclonal antibody (mAb) targeting HER2, is standard of care palliative 1st-line therapy for advanced HER2+ GEJ/GC patients (pts). M, an Fc-engineered anti-HER2 mAb, targets the same HER2 epitope but with higher affinity for both 158V (high binding) and 158F (low binding) alleles of activating Fc receptor CD16A. M coordinately enhanced both innate and adaptive immunity, including antigen-specific T-cell responses to HER2. PD-1 and LAG-3 are T-cell checkpoint molecules that suppress T-cell function. MGA012 (INCMGA00012) is a humanized, hinge-stabilized, IgG4 κ anti-PD-1 mAb blocking binding of PD-L1 or PD-L2 to PD-1. MGD013 is a humanized Fc-bearing bispecific tetravalent protein that binds to both PD-1 and LAG-3, inhibiting their respective ligand binding. We previously reported that a CTX-free regimen of M+PD-1 blockade was well tolerated in GEJ/GC pts, and induced a 30% objective response rate (ORR). This was 2- to 3-fold greater than in historical controls with checkpoint inhibitors alone. This registration-directed trial assesses efficacy, safety, and tolerability of M+checkpoint inhibition ± CTX in metastatic/locally advanced, treatment-naïve, HER2+ GEJ/GC pts. Methods: This is a 2-cohort, adaptive open-label phase 2/3 study. The first single arm, CTX-free cohort A evaluates M+MGA012 in HER2+ (immunohistochemistry [IHC] 3+) and PD-L1+ (excluding microsatellite instability high) pts. After 40 pts are evaluated for response/safety, 60 more pts will be enrolled if the threshold for continuation is met. In randomized cohort B, HER2+ (IHC 3+ or 2+/fluorescent in situ hybridization+) pts are enrolled irrespective of PD-L1 status. Part 1 randomizes pts to 1 of 4 arms (50 pts each): control arm (T+CTX) or 1 experimental arm (M+CTX; M+CTX+MGA012; M+CTX+MGD013). CTX is investigator’s choice XELOX or mFOLFOX-6. Part 2 consists of control (T+CTX) vs 1 experimental arm (M+CTX) + either MGA012 or MGD013, depending on results from part 1; with 250 pts each. The primary efficacy endpoint for cohort A (both parts) is ORR per RECIST 1.1; for cohort B part 2 it is overall survival.

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