ArticleCancer immunology, immunotherapy : CII2022
Treatment with a retinoic acid-inducible gene I (RIG-I) agonist as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: results from two phase 1 studies.
Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 27 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 I/II, Multicenter, Open-label, Clinical Trial of Intratumoral/Intralesional Administration of RGT100 in Subjects With Advanced or Recurrent Tumors
A Phase 1/1b, Open-label Clinical Study of Intratumoral/Intralesional Administration of MK-4621/JetPEI as Monotherapy or in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Solid Tumors
Who cites it
27 citing papers in PubMed, 31 citations in OpenAlex.
- Activating a B cell immune response regresses immunologically cold tumours.Nature nanotechnology · 2026Article
- A RIG-I targeting nanozyme induces PANoptosis for cancer immunotherapy.Nature communications · 2026Article
- Template-Directed RIG-I Agonist Assembly for Image-guided Targeted Cancer Immunotherapy.Molecular imaging and biology · 2026Article
- BRRIAR lncRNA alters breast cancer risk by modulating interferon signaling in cis and in trans.Molecular cancer · 2026Article
- Interplay between pathogen-mediated immune evasion and innate immune negative regulation in gastrointestinal tumors.Frontiers in immunology · 2026Review
- Innate immunity in tumour immunoediting and immunosurveillance.The EMBO journal · 2026Review
- Targeting innate immunity in cancer: mechanistic foundations, therapeutic vaccination, and clinical translation.Frontiers in immunology · 2026Review
- Anti-tumor analysis of the RIG-I agonist inBiochemistry and biophysics reports · 2025Article
- Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies.Acta pharmaceutica Sinica. B · 2025Review
- Lactate and lactylation in tumor immunity.Frontiers of medicine · 2025Review
- Overcoming Immune Therapy Resistance in Cancer Through Innate Immune Reprogramming.International journal of molecular sciences · 2025Review
- Fabrication of RIG-I-Activating Nanoparticles for Intratumoral Immunotherapy via Flash Nanoprecipitation.Molecular pharmaceutics · 2025Article
- Systemic administration of an RNA binding and cell-penetrating antibody targets therapeutic RNA to multiple mouse models of cancer.Science translational medicine · 2025Article
- Targeting Intracellular Innate RNA-Sensing Systems Overcomes Resistance to CAR T-cell Therapy in Solid Tumors.Cancer research · 2025Article
- The PARP inhibitor talazoparib synergizes with reovirus to induce cancer killing and tumour control in vivo in mouse models.Nature communications · 2025Article
- Clinical applications of oligonucleotides for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics.Immuno-oncology technology · 2025Review
- Innate immunity in tumors: roles and therapeutic targets.Frontiers in immunology · 2025Review
- Catch me if you can: viral nucleic acids to host sensors.Frontiers in immunology · 2025Review
- Advanced Nanotechnology-Based Nucleic Acid Medicines.Pharmaceutics · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe evaluated MK-4621, an oligonucleotide that binds and activates retinoic acid-inducible gene I (RIG-I), as monotherapy (NCT03065023) and in combination with the anti-programmed death 1 antibody pembrolizumab (NCT03739138). PATIENTS AND
methodsPatients were ≥ 18 years with histologically/cytologically confirmed advanced/metastatic solid tumors with injectable lesions. MK-4621 (0.2‒0.8 mg) was administered intratumorally as a stable formulation with jetPEI™ twice weekly over a 4-week cycle as monotherapy and weekly in 3-week cycles for up to 6 cycles in combination with 200 mg pembrolizumab every 3 weeks for up to 35 cycles. Primary endpoints were dose-limiting toxicities (DLTs), treatment-related adverse events (AEs), and treatment discontinuation due to AEs.
resultsFifteen patients received MK-4621 monotherapy and 30 received MK-4621 plus pembrolizumab. The only DLT, grade 3 pleural effusion that subsequently resolved, occurred in a patient who received MK-4621/jetPEI™ 0.8 mg plus pembrolizumab. 93% of patients experienced ≥ 1 treatment-related AE with both monotherapy and combination therapy. No patients experienced an objective response per RECIST v1.1 with MK-4621 monotherapy; 4 (27%) had stable disease. Three (10%) patients who received combination therapy had a partial response. Serum and tumor biomarker analyses provided evidence that MK-4621 treatment induced an increase in gene expression of interferon signaling pathway members and associated chemokines and cytokines.
conclusionsPatients treated with MK-4621 monotherapy or in combination with pembrolizumab experienced tolerable safety and modest antitumor activity, and there was evidence that MK-4621 activated the RIG-I pathway. At the doses tested, MK-4621 did not confer meaningful clinical benefit.
trial registrationClinicalTrials.gov, NCT03065023 and NCT03739138.
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Registered trials
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.