ArticleJournal for immunotherapy of cancer2023
First-in-human phase Ib trial of M9241 (NHS-IL12) plus avelumab in patients with advanced solid tumors, including dose expansion in patients with advanced urothelial carcinoma.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02994953 (A Phase Ib Open-Label, Dose-Finding Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Avelumab in Combination With M9241), which is not on this map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase Ib Open-Label, Dose-Finding Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Avelumab in Combination With M9241(NHS-IL12) in Subjects With Locally Advanced, Unresectable, or Metastatic Solid Tumors
Who cites it
26 citing papers in PubMed, 24 citations in OpenAlex.
- A Phase II Study of Docetaxel and Pembrolizumab plus Interleukin 12 Gene Therapy in Nonmetastatic, Anthracycline-Refractory Triple-Negative Breast Cancer (INTEGRAL).Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Programmed death-1 inhibition increases vaccine-induced T-cell infiltration in patients with prostate cancer.Journal for immunotherapy of cancer · 2025Trial
- A phase I trial of SON-1010, a tumor-targeted, interleukin-12-linked, albumin-binding cytokine, shows favorable pharmacokinetics, pharmacodynamics, and safety in healthy volunteers.Frontiers in immunology · 2024Trial
- Phase 1 study of KHK2455, a long-acting, potent and selective IDO1 inhibitor, in combination with avelumab in patients with locally advanced or metastatic urothelial carcinoma.Journal for immunotherapy of cancer · 2026Article
- Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances.Journal of hematology & oncology · 2026Review
- αHSA-proIL-12: A Tumor-Conditional IL-12 Prodrug with Reduced Systemic Toxicity and Potent Antitumor Activity.International journal of molecular sciences · 2026Article
- Oncolytic adenovirus co-expressing IL-12 and shVEGF potentiates immune checkpoint blockade for treatment of renal cell carcinoma: in vitro, organ-on-a-chip, and in vivo evaluation.Molecular medicine (Cambridge, Mass.) · 2026Article
- "Cytokine-Mediated tumor sensitization: mechanistic frameworks and therapeutic opportunities in cancer Immunotherapy".Clinical and experimental medicine · 2026Review
- Therapeutic application of IL-12 for cancer therapy.Translational cancer research · 2026Review
- Immunotherapy in clear cell renal cell carcinoma: current Status, novel Strategies, and future perspectives.Clinical and experimental medicine · 2026Review
- Cytokine delivery and targeting strategies in pet dogs with cancer: a comparative immuno-oncology approach.Frontiers in immunology · 2026Review
- Immunocytokines in cancer: a safety perspective.Frontiers in immunology · 2026Review
- Targeting IL-12 for pancreatic cancer immunotherapy: advances in delivery strategies and clinical translation.Frontiers in immunology · 2026Review
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- New frontiers in prostate cancer treatment from systemic therapy to targeted therapy.EMBO molecular medicine · 2025Review
- Cytokine Therapy in Bladder Cancer: Mechanisms, Efficacy, and Future Prospects.Current issues in molecular biology · 2025Review
- IL-12-producing cytokine factories induce precursor exhausted T cells and elimination of primary and metastatic tumors.Journal for immunotherapy of cancer · 2025Article
- Targeting PD-1Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- IL-12 minicircle delivery via extracellular vesicles as immunotherapy for bladder cancer.Cell proliferation · 2025Article
- Augmentation of Solid Tumor Immunotherapy With IL-12.The journal of gene medicine · 2024Review
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 5 countries.
Funding
Abstract
backgroundIn preclinical studies, combining M9241 (a novel immunocytokine containing interleukin (IL)-12 heterodimers) with avelumab (anti-programmed death ligand 1 antibody) resulted in additive or synergistic antitumor effects. We report dose-escalation and dose-expansion results from the phase Ib JAVELIN IL-12 trial investigating M9241 plus avelumab.
methodsIn the dose-escalation part of JAVELIN IL-12 (NCT02994953), eligible patients had locally advanced or metastatic solid tumors; in the dose-expansion part, eligible patients had locally advanced or metastatic urothelial carcinoma (UC) that had progressed with first-line therapy. Patients received M9241 at 4, 8, 12, or 16.8 µg/kg every 4 weeks (Q4W) plus avelumab 10 mg/kg every 2 weeks (Q2W, dose levels (DLs) 1-4) or M9241 16.8 µg/kg Q4W plus avelumab 800 mg once a week for 12 weeks followed by Q2W (DL5/dose expansion). Primary endpoints for the dose-escalation part were adverse events (AEs) and dose-limiting toxicities (DLTs), and those for the dose-expansion part were confirmed best overall response (BOR) per investigator (Response Evaluation Criteria in Solid Tumors V.1.1) and safety. The dose-expansion part followed a two-stage design; 16 patients were enrolled and treated in stage 1 (single-arm part). A futility analysis based on BOR was planned to determine whether stage 2 (randomized controlled part) would be initiated.
resultsAt data cut-off, 36 patients had received M9241 plus avelumab in the dose-escalation part. All DLs were well tolerated; one DLT occurred at DL3 (grade 3 autoimmune hepatitis). The maximum-tolerated dose was not reached, and DL5 was declared the recommended phase II dose, considering an observed drug-drug interaction at DL4. Two patients with advanced bladder cancer (DL2 and DL4) had prolonged complete responses. In the dose-expansion part, no objective responses were recorded in the 16 patients with advanced UC; the study failed to meet the criterion (≥3 confirmed objective responses) to initiate stage 2. Any-grade treatment-related AEs occurred in 15 patients (93.8%), including grade ≥3 in 8 (50.0%); no treatment-related deaths occurred. Exposures for avelumab and M9241 concentrations were within expected ranges.
conclusionsM9241 plus avelumab was well tolerated at all DLs, including the dose-expansion part, with no new safety signals. However, the dose-expansion part did not meet the predefined efficacy criterion to proceed to stage 2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.