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677 A phase 1, open-label, dose escalation study of the safety and tolerability of ANK-101 in advanced solid tumors

2024· article· en· W4404053144 on OpenAlexaff
Jong Chul Park, Marcus O. Butler, Brendan D. Curti, Gail Iodice, Danielle M. Pastor, Joseph Elassal, Howard L. Kaufman, John M. Kirkwood

Bibliographic record

VenueRegular and Young Investigator Award Abstracts · 2024
Typearticle
Languageen
FieldMedicine
TopicRadiopharmaceutical Chemistry and Applications
Canadian institutionsUniversity Health Network
Fundersnot available
KeywordsTolerabilityMedicinePharmacologyAdverse effect

Abstract

fetched live from OpenAlex

<h3>Background</h3> IL-12 is a cytokine that can stimulate both innate and adaptive tumor immunity. Clinical trials of systemic IL-12 have demonstrated anti-tumor activity, but potential efficacy has been markedly limited by significant systemic toxicity, including death. ANK-101 is an anchored immunotherapy that links IL-12 to aluminum hydroxide through an alum-binding protein (ABP). The ANK-101 complex anchors IL-12 in the tumor microenvironment (TME), resulting in prolonged local retention and low levels of systemic absorption. Preclinical studies in murine tumor models show that ANK-101 is retained at the injection site for up to 28 days, recruits and activates T and NK cells, promotes M1 myeloid cell differentiation, induces regression of both injected and un-injected tumors, and induces immunologic memory. <h3>Methods</h3> This first-in-human, open-label study aims to evaluate intratumoral ANK-101 in advanced solid malignancies in superficial (Part 1) and visceral (Part 2) tumors. Both parts have dose-escalation and expansion cohorts, with each enrolling 12–36 participants in dose escalation. The first three dose escalation cohorts for each part include single participant enrollment, followed by standard 3+3 dose escalation design. If no dose limiting toxicity (DLT) is observed, the dose level will be escalated until ≥1/3 or ≥2/6 patients experience a DLT. An additional ten patients will be enrolled at the recommended dose for expansion (RDE) in both Parts 1 and 2. Patients will be treated every 3 weeks for 4 cycles. Imaging or clinical assessments will be performed every 12 weeks in Part 1 and every 6 weeks in Part 2. If no significant clinical deterioration or unacceptable toxicity is apparent, patients may receive four additional cycles. Eligible participants must have an advanced solid malignancy that is refractory to standard treatment and accessible for injection and biopsy, measurable disease by RECIST v1.1, and ECOG PS of 0–1. Key exclusion criteria include tumors close to vital structures, uncontrolled bleeding disorders, and active autoimmune disease. Primary objectives include safety and tolerability and identification of the RDE. Secondary objectives include pharmacokinetics (PK) and immunogenicity (ADA) of ANK-101 and clinical activity measured by ORR, DCR, DOR, and PFS by RECIST v1.1. Exploratory objectives include QOL using FACT-G<sup>©</sup> and immune pharmacodynamic (PD) changes. PD assessments will include serum cytokines and circulating immune cells, and local levels of PD-L1, CD8+ T cells, and CD68+ macrophages, and changes in gene expression within the TME. This clinical trial is in progress. Clinical trial information: Clinical Trial Registry NCT06171750. Research Sponsor: Ankyra Therapeutics.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.535
Threshold uncertainty score0.387

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.041
GPT teacher head0.371
Teacher spread0.330 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations0
Published2024
Admission routes1
Has abstractyes

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