First‐in‐human phase 1 study of MK‐1248, an anti–glucocorticoid‐induced tumor necrosis factor receptor agonist monoclonal antibody, as monotherapy or with pembrolizumab in patients with advanced solid tumors

Cancer ◽  
2020 ◽  
Vol 126 (22) ◽  
pp. 4926-4935 ◽  
Author(s):  
Ravit Geva ◽  
Mark Voskoboynik ◽  
Konstantin Dobrenkov ◽  
Kapil Mayawala ◽  
Jennifer Gwo ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Necrosis Factor ◽  
Solid Tumors ◽  
Receptor Agonist ◽  
Tumor Necrosis ◽  
Phase 1 ◽  
Tumor Necrosis Factor Receptor ◽  
Advanced Solid Tumors ◽  
Phase 1 Study ◽  
Necrosis Factor

scholarly journals Phase 1 study of MEDI0562, a humanized OX40 agonist monoclonal antibody (mAb), in adult patients (pts) with advanced solid tumors

2016 ◽  
Vol 27 ◽  
pp. vi361 ◽  
Author(s):  
B.S. Glisson ◽  
R. Leidner ◽  
R.L. Ferris ◽  
J. Powderly ◽  
N. Rizvi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Solid Tumors ◽  
Phase 1 ◽  
Adult Patients ◽  
Advanced Solid Tumors ◽  
Phase 1 Study

scholarly journals A Phase 1 Study of Necitumumab (Anti-Egfr Monoclonal Antibody) in Japanese Patients with Advanced Solid Tumors

2014 ◽  
Vol 25 ◽  
pp. v70 ◽  
Author(s):  
Hiroshi Nokihara ◽  
Noboru Yamamoto ◽  
Yosuke Tamura ◽  
Yuko Tanabe ◽  
Kazunori Honda ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Solid Tumors ◽  
Phase 1 ◽  
Japanese Patients ◽  
Advanced Solid Tumors ◽  
Phase 1 Study

Abstract 2506: A phase 1 study of ABT-806, a humanized recombinant anti-EGFR monoclonal antibody, in patients with advanced solid tumors

2012 ◽  
Author(s):  
James M. Cleary ◽  
Lorrin Kwock-Chong Yee ◽  
Nilofer Azad ◽  
Michael Carducci ◽  
David Cosgrove ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Solid Tumors ◽  
Phase 1 ◽  
Advanced Solid Tumors ◽  
Phase 1 Study

A phase Ib study to assess the safety of lexatumumab, a human monoclonal antibody that activates TRAIL-R2, in combination with gemcitabine, pemetrexed, doxorubicin or FOLFIRI

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14006-14006 ◽  
Author(s):  
B. I. Sikic ◽  
H. A. Wakelee ◽  
M. von Mehren ◽  
N. Lewis ◽  
A. H. Calvert ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Human Monoclonal Antibody ◽  
Single Agent ◽  
Tumor Necrosis Factor Receptor ◽  
Chemotherapeutic Agents ◽  
Extrinsic Pathway ◽  
Wide Range ◽  
Necrosis Factor

14006 Background: Lexatumumab (HGS-ETR2) is a fully-human agonistic monoclonal antibody that targets and activates the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor 2 (TRAIL-R2). TRAIL-R2 is a member of the Tumor Necrosis Factor Receptor (TNFR) superfamily that, when activated, induces apoptosis via the extrinsic pathway. Lexatumumab shows promising anti-tumor activity in preclinical models, particularly in combination with chemotherapeutic agents. Single-agent lexatumumab was well-tolerated in phase I trials. This is the first study of the safety of a TRAIL-R2 agonist in combination with chemotherapy. Methods: Patients for whom gemcitabine, pemetrexed, doxorubicin or FOLFIRI was considered an appropriate treatment received one of the full-dose chemotherapy regimens plus lexatumumab every 2 weeks (for gemcitabine and FOLFIRI) or 3 weeks (for pemetrexed and doxorubicin). Four to 6 patients were treated with 5 mg/kg lexatumumab in each chemotherapy cohort prior to dose escalation to 10 mg/kg. Results: To date, 41 patients with a wide range of cancer types have received 164 courses of lexatumumab over the 2 dose levels. The majority (33/41) received at least 2 courses (range 1 to 19). Lexatumumab was well-tolerated; no dose reductions of lexatumumab were required. Severe adverse events considered at least possibly related to lexatumumab included anemia, fatigue and dehydration. Tumor shrinkage has been observed, including confirmed partial responses (PRs) in the FOLFIRI and doxorubicin arms. Eight patients continue on study. Conclusions: Lexatumumab can be safely administered in combination with a wide range of chemotherapeutic agents. Evaluation of the efficacy of lexatumumab in combination with chemotherapy in Phase 2 trials is warranted. [Table: see text]

A phase 1b study of the anti-PD-1 monoclonal antibody BGB-A317 (A317) in combination with the PARP inhibitor BGB-290 (290) in advanced solid tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3013-3013 ◽  
Author(s):  
Michael Friedlander ◽  
Tarek Meniawy ◽  
Ben Markman ◽  
Linda R. Mileshkin ◽  
Paul R. Harnett ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Monoclonal Antibody ◽  
Solid Tumors ◽  
Phase 1 ◽  
Parp Inhibitor ◽  
Single Agent ◽  
Advanced Solid Tumors ◽  
Phase 1 Study ◽  
Multiple Tumor ◽  
Study Results

3013 Background: The release of tumor-associated antigens may enhance the response to immunotherapy. BGB-A317, a humanized IgG4 variant monoclonal antibody engineered to have no Fc gamma receptor binding, targets the programmed cell death-1 (PD-1) receptor. It is being developed in solid and hematologic malignancies at a dose of 200 mg IV Q3W. BGB-290, a potent inhibitor of PARP 1/2, is hypothesized to promote neoantigen release that will potentially increase the efficacy of BGB-A317. A phase 1 study identified 60mg BID as the recommended Phase 2 dose (RP2D) for BGB-290. This study consists of initial dose escalation to determine the maximum-tolerated dose (MTD), safety, PK profile, and preliminary anti-tumor activity of the combination, followed by expansion into ovarian, breast, prostate, gastric, bladder, pancreatic and small cell lung cancers. Methods: Cohorts of 6 -12 pts with advanced solid tumors were treated in each of 5 planned dose levels (DLs). In DLs 1-3, BGB-290 doses ranged between 20-60mg PO BID with BGB-A317 2mg/kg IV Q3W. In DLs 4 - 5, BGB-290 doses were 40 or 60 mg BID; A317 was given at 200 mg IV Q3W based on PK data from a single agent Phase 1 study. Results: As of 16 Jan 2017, 38 pts [median age 59 years (34-75)] were treated in DLs 1-4; enrollment to DL5 is ongoing. One DLT of persistent Gr 2 nausea was reported in DL 4. The most common adverse event (AE) considered related to both study drugs was fatigue (10.5%). Immune-related AEs were Gr 3 hypophysitis (n = 1), Gr 3 or 4 autoimmune hepatitis(n = 2), and Gr 2 elevated AST/ALT (n = 1). Decreases in tumor burden have been observed in 16 pts; 7 achieved a PR (5 with ovarian and one each with uterine and pancreatic cancer) and one CR was observed in ovarian cancer. Six pts had SD for > 6 months including 2 pts with pancreatic cancer who received BGB-A317+BGB-290 for 189 and 281 days. Plasma/serum exposure of BGB-290 and BGB-A317 were consistent with those in single-agent trials. Conclusions: BGB290 and BGB-A317 can be combined. Dose expansion in multiple tumor types is planned to commence in 2017 once the RP2D is determined. Clinical trial information: NCT02660034.

A phase 1b study of the anti-PD-1 monoclonal antibody BGB-A317 (A317) in combination with the PARP inhibitor BGB-290 (290) in advanced solid tumors.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 48-48 ◽  
Author(s):  
Michael Friedlander ◽  
Tarek Meniawy ◽  
Ben Markman ◽  
Linda R. Mileshkin ◽  
Paul Harnett ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Autoimmune Hepatitis ◽  
Solid Tumors ◽  
Phase 1 ◽  
Parp Inhibitor ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Advanced Solid Tumors ◽  
Phase 1 Study ◽  
Study Results

48 Background: The release of tumor-associated antigens may enhance the response to immunotherapy. BGB-A317, a humanized IgG4 variant monoclonal antibody engineered to have no Fc gamma receptor binding, targets the programmed cell death-1 (PD-1) receptor. It is being developed in solid and hematologic malignancies at a dose of 200 mg IV Q3W. BGB-290, a potent inhibitor of PARP 1/2, is hypothesized to promote neoantigen release that may potentially increase the efficacy of BGB-A317. A phase 1 study identified 60 mg BID as the recommended Phase 2 dose (RP2D) for BGB-290. This study consists of initial dose escalation to determine the maximum-tolerated dose (MTD), safety, pharmacokinetic (PK) profile, and preliminary antitumor activity of the combination, followed by expansion into ovarian, breast, prostate, gastric, bladder, pancreatic and small cell lung cancers. Methods: Cohorts of 6–12 patients with advanced solid tumors were treated in each of 5 planned dose levels (DLs). In DLs 1–3, BGB-290 doses ranged between 20–60 mg PO BID with BGB-A317 2 mg/kg IV Q3W. In DLs 4–5, BGB-290 doses were 40 or 60 mg BID; A317 was given at 200 mg IV Q3W based on PK data from a single agent Phase 1 study. Results: As of 31 March 2017, 43 patients [median age 63 years (34–75)] were treated in DLs 1–5. Three patients experienced four dose-limiting toxicities: grade 2 nausea (DL4), grade 2 nausea and grade 2 vomiting (DL5), and grade 4 autoimmune hepatitis (DL5). MTD was identified as BGB-A317 200 mg IV Q3W + BGB-290 40 mg PO BID. The most common adverse event (AE) considered related to both study drugs was fatigue. Immune-related AEs of Grade ≥3 were elevated alanine aminotransferase/aspartate aminotransferase (n = 3), autoimmune hepatitis (n = 3), and hepatitis (n = 1). Complete or partial response was observed in 11 patients, 4 of whom had confirmed PR or CR. Plasma/serum exposure of BGB-290 and BGB-A317 were consistent with those in single-agent trials. Conclusions: The combination of BGB-A317 and BGB-290 was generally well tolerated in patients with advanced solid tumors. These results support the continuation of this trial with enrollment into the disease-specific cohorts. Clinical trial information: NCT02660034.

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