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

2024· article· en· W4400265274 on OpenAlexaff
Jong Chul Park, Marcus O. Butler, Brendan D. Curti, Leisha A. Emens, Danielle M. Pastor, Joseph Elassal, Howard L. Kaufman, John M. Kirkwood

Bibliographic record

VenueJournal of Clinical Oncology · 2024
Typearticle
Languageen
FieldMedicine
TopicLung Cancer Treatments and Mutations
Canadian institutionsPrincess Margaret Cancer CentreUniversity of Toronto
Fundersnot available
KeywordsTolerabilityMedicineOpen labelOpen label studyMaximum tolerated doseOncologyInternal medicineAdverse effect

Abstract

fetched live from OpenAlex

TPS2689 Background: IL-12 is a cytokine that can stimulate both innate and adaptive tumor immunity. Clinical trials of intravenous IL-12 demonstrated anti-tumor activity limited by significant systemic toxicity, including patient deaths. 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 showed 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. Methods: This is a first-in-human, open-label dose escalation study of ANK-101 in advanced solid tumors with a planned sample size of 12-36 participants. The first three dose escalation cohorts include a single participant, and then study enrollment follows a 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). Participants will be treated with intratumoral ANK-101 every 3 weeks for 4 cycles. Imaging or clinical assessments will be performed at week 12. If there is no significant clinical deterioration or unacceptable toxicity at this visit, participants may receive four more cycles. Eligible patients must have an advanced solid malignancy refractory to standard treatment and be 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 of the study are to determine the safety and tolerability of ANK-101 and identify the RDE. Secondary objectives include pharmacokinetics (PK) and immunogenicity (ADA) of ANK-101 and clinical activity as measured by ORR, DCR, DOR and PFS by RECIST v1.1. Exploratory objectives include assessment of QOL using FACT-G and profiling immune-based 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: NCT06171750 .

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)0.002
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 score0.007
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0030.001
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0010.000
Science and technology studies0.0010.001
Scholarly communication0.0010.002
Open science0.0010.000
Research integrity0.0020.004
Insufficient payload (model declined to judge)0.0070.002

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 head0.158
GPT teacher head0.582
Teacher spread0.425 · 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

Citations0
Published2024
Admission routes1
Has abstractyes

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