scholarly journals Clinical Activity of AK002, an Anti-Siglec-8 Monoclonal Antibody, in Treatment-Refractory Chronic Urticaria

2020 ◽  
Vol 145 (2) ◽  
pp. AB239 ◽  
Author(s):  
Sabine Altrichter ◽  
Petra Staubach ◽  
Malika Pasha ◽  
Henrik Rasmussen ◽  
Bhupinder Singh ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Chronic Urticaria ◽  
Clinical Activity ◽  
Treatment Refractory

BEGONIA: Phase 1b/2, open-label, platform study of the safety and efficacy of durvalumab (D) ± paclitaxel (P) with novel oncology therapies for first-line metastatic triple-negative breast cancer (mTNBC): Addition of arm 7, D + datopotamab deruxtecan (Dato-DXd; DS-1062).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS1105-TPS1105
Author(s):  
Peter Schmid ◽  
Ana Tablante Nunes ◽  
Hannah Dry ◽  
Rachel Dougherty ◽  
Vatsala Karwe ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Primary Endpoint ◽  
Topoisomerase I ◽  
Objective Response ◽  
Locally Advanced ◽  
Clinical Activity ◽  
First Line ◽  
Safety And Efficacy ◽  
Topoisomerase I Inhibitor ◽  
Heavily Pretreated

TPS1105 Background: Patients (pts) with mTNBC have limited treatment options and poor prognosis. The combination of immune checkpoint inhibitors with chemotherapy shows promise, but only a subset of pts with mTNBC derive benefit, highlighting the need for new combinations. BEGONIA is an ongoing Simon 2-stage, multicenter, multi-arm platform study evaluating the safety and efficacy of D, an anti–PD-L1 monoclonal antibody, with or without P, in combination with novel oncology therapies as first-line treatment for mTNBC (NCT03742102). Dato-DXd is an antibody-drug conjugate (ADC) consisting of a humanized anti-trophoblast cell surface antigen 2 (TROP2) IgG1 monoclonal antibody, a stable tetrapeptide-based cleavable linker, and a topoisomerase I inhibitor payload. Dato-DXd displayed encouraging clinical activity with a manageable safety profile in heavily pretreated pts with metastatic NSCLC in the phase 1 TROPION-PanTumor01 (NCT03401385) study. TROP2 is highly expressed on breast and other epithelial tumors, and a TROP2 ADC showed activity in heavily pretreated pts with mTNBC (Bardia, NEJM 2019). Methods: Eligible female pts are aged ≥18 years with untreated unresectable, locally advanced or mTNBC, ≥12 months since prior taxane therapy, ECOG PS 0/1, adequate organ function, and ≥1 nonirradiated measurable lesion. For Arm 7, pts are excluded if they have clinically significant corneal disease, history of interstitial lung disease/pneumonitis, underlying pulmonary disorder, or prior treatment with an ADC containing a topoisomerase I inhibitor. Arm 7 will evaluate D (1120 mg) + Dato-DXd (6 mg/kg) given intravenously every 3 weeks until disease progression or unacceptable toxicity. Part 1 of each arm includes a total of 30 pts with a safety run-in (n=6) to observe dose-limiting toxicities, identify the recommended phase 2 dose (RP2D), and detect an efficacy signal for part 1 expansion. The primary endpoint of part 1 is safety and tolerability. Secondary endpoints include investigator-assessed objective response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS). Once the RP2D has been established for part 1, a futility analysis will be performed with an option to expand the cohort to an additional 27 pts if expansion criteria are met. The primary endpoint for part 1 is ORR. Tumors will be assessed every 6 weeks per RECIST v1.1. Kaplan-Meier analysis will be used for PFS and OS. PD-L1 and TROP2 expression will be assessed by immunohistochemistry. Enrollment is ongoing. Clinical trial information: NCT03742102 .

Gemcitabine (Gem) and nab-paclitaxel (NP) ± nivolumab (nivo) ± CD40 agonistic monoclonal antibody APX005M (sotigalimab), in patients (Pts) with untreated metastatic pancreatic adenocarcinoma (mPDAC): Phase (Ph) 2 final results.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4019-4019
Author(s):  
Mark H. O'Hara ◽  
Eileen Mary O'Reilly ◽  
Robert A. Wolff ◽  
Zev A. Wainberg ◽  
Andrew H. Ko ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Type I Error ◽  
Acute Hepatic Failure ◽  
Tumor Burden ◽  
Clinical Activity ◽  
Tumor Biomarker ◽  
Type I ◽  
Open Label ◽  
Comparison Results ◽  
Biomarker Analysis

4019 Background: Results from a ph1b trial evaluating gem/NP with CD40 agonistic monoclonal antibody APX005M ± nivo demonstrated promising clinical activity in pts with untreated mPDAC (O’Hara 2021). Herein, we report results from the follow-on, randomized (rand) ph2 trial evaluating gem/NP ± nivo ± APX005M. Methods: Pts with untreated mPDAC were rand to 1 of 3 open-label arms: gem/NP/nivo (A), gem/NP/APX005M (B), gem/NP/nivo/APX005M (C). All pts were treated with 1000 mg/m2 gem and 125 mg/m2 NP. Patients received 240 mg nivo in arms A and C and 0.3 mg/kg APX005M (RP2D) IV in arms B and C. Ph1b pts were included in ph2 analyses. 1° endpoint: 1-year OS rate of each arm, compared to a 35% historical OS rate for gem/NP (Von Hoff 2013). Key 2° endpoints: ORR, DCR, DOR, PFS and safety. Tumor and blood were collected for biomarker analysis. Planned enrollment of 35 pts/arm provided 81% power for testing the alternative of 58% OS rate vs 35%, using a 1-sided, 1-sample Z test with 5% type I error. Trial was not powered for cross-arm comparison. Results: 93 pts were rand in ph2 (N = 34, 30, 29 to A, B, C); when ph1b pts included, a total of 105 pts (34, 36, 35) were analyzed for efficacy and 108 pts (36, 37, 35) for safety. Min follow-up was 14 months (mos). Baseline characteristics were balanced across arms, inclusive of tumor burden, presence of liver metastases and stage at initial diagnosis (stage 1-3 vs 4). 1-year OS rate was 57% (1-sided p = 0.007 vs 35% historical rate, 95% lower CI bound = 41%) for A, 51% (p = 0.029, 95% bound = 36%) for B and 41% (p = 0.236, 95% bound = 27%) for C. Median OS and secondary endpoints are listed in Table. TRAE rates were similar across arms and to ph1b. 8 (7%) pts experienced an AE leading to tx discontinuation (6, 1, 1 in A, B, C), 40 (37%) pts experienced a serious TRAE (14, 15, 11 in A, B, C) and 2 pts died due to TRAEs; 1 each in B (acute hepatic failure) and C (intracranial hemorrhage). Conclusions: In this ongoing, seamless ph1b/2 trial of gem/NP ± nivo ± APX005M in pts with mPDAC, antitumor activity was observed in all arms. 1° endpoint of 1-year OS > 35% was met when combining gem/NP with either nivo or APX005M; however, not the combination. Safety was manageable; consistent with ph1b. Detailed multiomic immune and tumor biomarker analyses are underway to elucidate mechanisms of action and inform pt subsets that benefit most from these combinations. Clinical trial information: NCT03214250. [Table: see text]

scholarly journals Safety and clinical activity of MEDI0562, a humanized OX40 agonist monoclonal antibody, in adult patients with advanced solid tumors

2018 ◽  
Vol 29 ◽  
pp. viii410 ◽  
Author(s):  
B. Glisson ◽  
R. Leidner ◽  
R.L. Ferris ◽  
J. Powderly ◽  
N.A. Rizvi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Solid Tumors ◽  
Adult Patients ◽  
Clinical Activity ◽  
Advanced Solid Tumors

scholarly journals MA09.02 In Vivo, Ex Vivo and Early Clinical Activity of EGFR Monoclonal Antibody and Osimertinib in EGFR Exon 20 Insertion NSCLC

2019 ◽  
Vol 14 (10) ◽  
pp. S282
Author(s):  
J. Riess ◽  
N. Floch ◽  
P. Mack ◽  
M. Martin ◽  
D. Vang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Ex Vivo ◽  
Clinical Activity ◽  
Exon 20

First use of alemtuzumab in Balo’s concentric sclerosis: a case report

2013 ◽  
Vol 19 (12) ◽  
pp. 1673-1675 ◽  
Author(s):  
JWL Brown ◽  
AJ Coles ◽  
JL Jones
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Standard Protocol ◽  
Demyelinating Disorder ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Radiological Impact ◽  
Treatment Refractory ◽  
Baló’S Concentric Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Balo’s concentric sclerosis (BCS) is a rare demyelinating disorder of the central nervous system. The humanised monoclonal antibody alemtuzumab has shown efficacy in another demyelinating disorder, relapsing–remitting multiple sclerosis. We aimed to explore its efficacy in treatment-refractory BCS. A 52-year-old male with radiologically confirmed progressive BCS resistant to steroids, plasmapharesis and cyclophosphamide was administered a standard protocol of alemtuzumab. Treatment failed to slow his decline; he died 6 months after administration. Why alemtuzumab induced no clinical or radiological impact may be multifactorial. We review the evidence directing BCS therapy and propose the next steps for exploring this potentially fatal condition.

DREAMM-6: Safety and tolerability of belantamab mafodotin in combination with bortezomib/dexamethasone in relapsed/refractory multiple myeloma (RRMM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8502-8502 ◽  
Author(s):  
Ajay K. Nooka ◽  
Keith Stockerl-Goldstein ◽  
Hang Quach ◽  
Adam Forbes ◽  
Maria-Victoria Mateos ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Safety Profile ◽  
Single Agent ◽  
Clinical Activity ◽  
Blurred Vision ◽  
Split Dose ◽  
Prior Therapy ◽  
B Cell Maturation ◽  
Previously Treated ◽  
Combination Regimens

8502 Background: Belantamab mafodotin, a B-cell maturation antigen targeting immunoconjugate, demonstrated clinically meaningful, single-agent activity in patients with heavily pre-treated RRMM refractory to an immunomodulatory agent, a proteasome inhibitor, and refractory and/or intolerant to an anti-CD38 monoclonal antibody (DREAMM-2, NCT03525678, Lancet Oncol.2020). The multimodal mechanism of action and manageable safety profile make belantamab mafodotin a promising candidate for use in different RRMM combination regimens. Methods: DREAMM-6 (NCT03544281) is an ongoing, two-part, two-arm, study evaluating the safety, tolerability, and clinical activity of belantamab mafodotin in combination with bortezomib/dexamethasone (BorDex) and lenalidomide/dexamethasone in patients previously treated with ≥1 prior therapy line. Here, we present data for belantamab mafodotin in combination with BorDex. Part 1 (dose escalation) and Part 2 (dose expansion) evaluated belantamab mafodotin (2.5 and 3.4 mg/kg) administered as SINGLE (Day 1) or SPLIT dose (divided equally on Days 1 and 8) in combination with BorDex. Results: As of February 6, 2020, 52 patients were enrolled: 6 patients were enrolled at 2.5 mg/kg single dose and 7 at 3.4 mg/kg single dosing in Part 1, and 45 patients in Part 2. No dose-limiting toxicities were observed. Corneal events (including keratopathy, blurred vision, and dry eye) and thrombocytopenia were the most frequently reported AEs and were clinically manageable. Conclusions: In DREAMM-6, preliminary data demonstrate that the combination of belantamab mafodotin and BorDex has an acceptable safety profile, with no new safety signals identified. Funding: GlaxoSmithKline (207497). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03544281 .

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