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A phase Ib study of IMU-131 HER2/neu peptide vaccine plus chemotherapy in patients with HER2/neu overexpressing metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction.

2019· article· en· W2947511888 on OpenAlexaff
Yee Chao, Thomas Yau, Marina Maglakelidze, Iurie Bulat, Suebpong Tanasanvimon, Chaiyut Charoentum, Wichit Arpornwirat, Jedzada Maneechavakajorn, Arunee Dechaphunkul, Teerapat Ungtrakul, Chia‐Jui Yen, Li‐Yuan Bai, Wen‐Chi Chou, Ursula Wiedermann, Anthony J. Good, Nick Ede, Leslie Chong

Bibliographic record

VenueJournal of Clinical Oncology · 2019
Typearticle
Languageen
FieldMedicine
TopicMonoclonal and Polyclonal Antibodies Research
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsMedicineCapecitabineTolerabilityImmunogenicityHER2/neuInternal medicineTrastuzumabCancerOncologyPeptide vaccineChemotherapyGastroenterologyBreast cancerAdjuvantAntibodyImmunologyEpitopeAdverse effectColorectal cancer

Abstract

fetched live from OpenAlex

4030 Background: Gastric cancer is the 5th most common cancer and the 3rd leading cause of cancer deaths. HER2/neu is overexpressed in 15% - 25% of patients with gastric cancer. Monoclonal antibodies against HER2/neu are effective but alternatives are needed due to cost and global availability. IMU-131 is a B-cell peptide vaccine composed of a fusion of 3 epitopes from the extracellular domain of HER2/neu conjugated to CRM197 with the adjuvant Montanide. Polyclonal antibodies against IMU-131 peptides elicit antitumor activity in vitro and a phase I study demonstrated safety and immunogenicity in Her-2 +/++ breast cancer patients. Methods: IMU-131 was given to patients with HER2/neu overexpressing gastric or gastroesophageal junction (GEJ) adenocarcinoma in an international open-label Phase 1b dose escalation trial performed in 14 Asian and Eastern European sites assessing safety, tolerability, and immunogenicity. Each patient received IMU-131 on Days 0, 14, and 35, accompanied by cisplatin and 5-fluorouracil or capecitabine every 21 days. Results: 14 patients were enrolled with advanced stage IIIb or IV with 10 HER2 overexpressing tumors (7 x HER2+++, 3 x HER2++ FISH positive) and 4 HER2++ expressing tumors. Mean age was 57 yo (range of 21 - 79) with ECOG scores of 0 or 1 in 7 patients each. There were 9 Asian and 5 Caucasian patients with 5 females and 9 males. Dose levels were 0.1, 0.3 and 0.5 mg with 3, 6, and 5 patients receiving those dose levels each. 11 patients received all 3 doses with 3 patients who received only 2 doses due to disease progression and 2 patients received a dose on day 182. Of the 14 patients dosed 11 were evaluable for tumor progression at day 56 and later. Of those patients, the best response was 1 CR, 4 PR,5 SD and 1 PD. In the 0.1 mg dose group the best response was 1 CR and 2 SD, with 2 PR, 2 SD and 1 PD in the 0.3 mg group and 2 PR and 1 SD in the 0.5 mg group. In patients with HER2 overexpression there was 1 CR, 4 PR, 2 SD and 1 PD, and in patients with HER2++ expression there was 3 SD. There were no SAEs related to IMU-131 and 1 patient had a mild injection site reaction. Conclusions: IMU-131 is a promising B-Cell vaccine against HER2. Further work in a controlled phase 2 trial is ongoing. Clinical trial information: NCT02795988.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.074
GPT teacher head0.454
Teacher spread0.379 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2019
Admission routes1
Has abstractyes

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