tolododekin alfa (ANK-101) / Ankyra Therap - LARVOL DELTA

A phase 1b, two-arm study of tolododekin alfa (ANK-101) in combination with an anti–PD-1/PD-L1 antibody in participants with advanced non–small cell lung cancer (NSCLC). (ASCO 2026) - P1 | "In Cohort A, participants will receive tolododekin alfa at 250 µg/mL IT in combination with cetrelimab (anti-PD-1) intravenously (IV) Q3W at a dose of 360 mg for up to 8 cycles, followed by cetrelimab monotherapy for up to one year, unless they have unacceptable toxicity, clinical deterioration, confirmed tumor progression, or have withdrawn consent. This clinical trial is in progress. Clinical trial information: NCT07027514."

Combination therapy • IO biomarker • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD8 • EGFR • IL12A

A Study of Tolododekin Alfa (ANK-101) in Renal Allograft Recipients With High Risk Cutaneous Squamous Cell Carcinoma (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Ankyra Therapeutics, Inc | N=20 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Transplantation

Researchers and clinicians from the Mount Sinai Tisch Cancer Center will present new research at the 2026 Annual Meeting of the American Society of Clinical Oncology (ASCO), taking place Friday, May 29, through Tuesday, June 2, at McCormick Place in Chicago. (Mount Sinai Cancer)

P1 data • P3 data • Retrospective data • Trial status • Head and Neck Cancer • Non Small Cell Lung Cancer • Urothelial Cancer

Quality of life in cancer patients treated with anchored interleukin-12 (IL-12) immunotherapy: Results from a first-in-human phase 1 trial of tolododekin alfa (ANK-101). (ASCO 2026) - P1 | "ANK-101, the first anchored immunotherapy, was associated with QOL scores that were not significantly diminished in heavily pre-treated advanced cancer patients with a non-significant decrease in social and physical well-being among those who developed grade 2 or greater adverse events. Further, patients with visceral tumors had no difference in QOL compared to superficial lesions. Early implementation of QOL data is feasible in phase 1 trials and may be of use to identify drug impact on clinical and safety measures."

Clinical • First-in-human • HEOR • P1 data • Colorectal Cancer • Dental Disorders • Melanoma • Neutropenia • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Stomatitis • IL12A

Ankyra Therapeutics Announces Presentations on Novel IL-12 Anchored Immunotherapy at 2026 ASCO (Businesswire) - "The presentations highlight ongoing Phase 1 clinical trials of tolododekin alfa, a novel IL-12 anchored immunotherapy, including a trial-in-progress poster describing its evaluation in combination with an anti-PD-1/PD-L1 antibody in people with advanced non-small cell lung cancer (NSCLC), as well as baseline quality-of-life data from a separate Phase 1 trial of tolododekin alfa in people with advanced or metastatic solid tumors."

P1 data • Trial status • Non Small Cell Lung Cancer

Immune escape via myeloid-derived suppressor cells in solid tumor cancer patients treated with anchored IL-12? (tolododekin alfa) (AACR 2026) - P1 | "Tolododekin alfa promotes intratumoral infiltration of CD8+ T cells, more prominent in patients who achieved disease control with anchored IL-12. Conversely, there is a compensatory recruitment of MDSCs, particularly M-MDSCs, in patients with progressive disease. MDSC expansion as a mechanism of immune escape merits additional mechanistic studies to define drivers of MDSC recruitment and inform rational therapeutic combinations."

Clinical • IO biomarker • Myeloid-derived suppressor cells • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD14 • CD8 • IL12A • ITGAM • PD-L1

Intratumoral IL-12 in combination with HDAC inhibition overcomes checkpoint-refractory tumors (AACR 2026) - "In this study, we investigated the anti-tumor activity and mechanism of action of murine ANK-101 (mANK-101) delivered intra-tumorally in combination with the class I histone deacetylase (HDAC) inhibitor entinostat, in different ICB-refractory murine tumor models, including CT26 (colorectal) and MOC-1 (HPV16neg head and neck). Mice receiving Entinostat diet and/or mANK-101 were monitored for anti-tumor activity, survival and protective memory. Collectively, these findings provide a rationale for the combination of intratumoral delivery of anchored IL-12 with epigenetic modulation for patients with ICB-refractory solid tumors, such as colorectal and HPV16neg head and neck cancers."

Combination therapy • Head and Neck Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL12A • KRAS • TNFA

Ankyra Therapeutics Announces Clinical Presentations on Novel IL-12 Anchored Immunotherapy at AACR 2026 (Businesswire) - "The presentations cover data from the ongoing Phase 1 clinical trial of tolododekin alfa, a novel IL-12 anchored immunotherapy, and preclinical data on anchored immunotherapy in combination with HDAC for the treatment of checkpoint-refractory solid tumors."

P1 data • Preclinical • Solid Tumor

Results of a first-in-human phase 1 trial of anchored IL-12 drug conjugate (ANK-101) (AACR 2025) - P1 | "ANK-101 is well tolerated at doses tested, demonstrated biologic activity, and was associated with durable disease control across different tumors in a heavily pretreated population. Further investigation is warranted."

First-in-human • IO biomarker • P1 data • Bladder Cancer • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IFNG • IL12A • PD-L1

Anchored IL-12 synergizes with an epigenetic modulator to promote immune remodeling and overcome anti-PD1-refractory murine tumors (AACR 2024) - "Significant decrease in CD4+ Tregs and increased CD8/Treg ratio were also observed. Ongoing functional studies, proteomic and immune cell analysis at the tumor site, tdLN, and periphery, including single cell transcriptomics and epigenetic studies, will allow for a deeper understanding of the synergistic effect of mANK-101 with the epigenetic modulator Entinostat.Conclusions Collectively, these findings form a rationale for the clinical combination of intralesional delivery of ANK-101 with entinostat for patients with ICB-refractory malignancies, including colorectal and HPV16neg head and neck cancers."

Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL12A • KRAS • TNFA

Alum-anchored IL-12 combined with HDAC inhibition overcomes checkpoint blockade refractory tumors (AACR-IO 2026) - "In this study, we investigated the anti-tumor activity and mechanism of action of murine ANK-101 (mANK-101) delivered intra-tumorally in combination with the class I histone deacetylase (HDAC) inhibitor entinostat, in different ICB-refractory murine tumor models, including CT26 (colorectal) and MOC-1 (HPV16 neg head and neck). Collectively, these findings provide a rationale for the combination of intratumoral delivery of anchored IL-12 with epigenetic modulation for patients with ICB-refractory solid tumors, such as colorectal and HPV16 neg head and neck cancers. Citation Format: Asma S. Khelifa, Christine M. Minnar, Katherine E. Lothstein, Masaya Miyamoto, Ainara Meler, Nicholas Roller, Lisa K. Poppe, David Peeney, Sailaja Battula, Howard L. Kaufman, Jeffrey Schlom, Sofia R. Gameiro. Alum-anchored IL-12 combined with HDAC inhibition overcomes checkpoint blockade refractory tumors [abstract]."

Checkpoint block • Checkpoint inhibition • Head and Neck Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL12A • KRAS • TNFA

Ankyra Therapeutics Announces First Patient Dosed in Phase 1b Trial Evaluating First-in-Class Anchored Immunotherapy in Combination with Immune Checkpoint Blockade in Patients with Lung Cancer (Businesswire) - "This study will evaluate the combination of Ankyra’s tolododekin alfa (ANK-101), an anchored IL-12 drug conjugate with the anti-PD1 agent, cetrelimab, in patients who have progressed after initial treatment of metastatic, non-mutated non-small cell lung cancer (NSCLC). In addition, the study will evaluate tolododekin alfa in combination with standard of care immune checkpoint blockade in first-line treatment of patients with metastatic, non-mutated NSCLC and a tumor proportion score (TPS) of ≥ 50%."

Trial status • Non Small Cell Lung Cancer

Intratumoral IL-12 in combination with HDAC inhibition overcomes checkpoint-refractory tumors (SITC 2025) - "In this study, we investigated the anti-tumor activity and mechanism of action of murine ANK-101 (mANK-101) delivered intratumorally in combination with the class I histone deacetylase (HDAC) inhibitor entinostat, in different ICB-refractory murine tumor models, including CT26 (colorectal) and MOC-1 (HPV16neg head and neck).Methods Mice receiving Entinostat diet and/or mANK-101 were monitored for anti-tumor activity, survival and protective memory. Notably, spatial analysis of tumor architecture indicates the development of B-cell rich stemness hubs exclusive to combination therapy. Ongoing in-depth studies including single cell transcriptomics in the tumor and tDLN, and investigation of the role of immune stemness hubs in the observed anti-tumor activity will allow for an in-depth understanding of the synergistic effect of mANK-101 with HDAC inhibition.Conclusions Collectively, these findings provide a rationale for the combination of intratumoral delivery of anchored..."

Combination therapy • Head and Neck Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL12A • KRAS • TNFA

Baseline NKT cells as a potential predictive biomarker for treatment with an anchored IL-12 drug conjugate in patients with solid tumors (SITC 2025) - P1 | "ANK-101 (tolododekin alfa) is an alum-anchored IL-12 drug conjugate designed to deliver and retain high doses of IL-12 in solid tumors...Higher baseline NKT cells were associated with disease control. Further studies are warranted to better define if NKT cells may serve as a predictive biomarker for IL-12 immunotherapy."

Biomarker • Clinical • IO biomarker • Oncology • Solid Tumor • CD8 • IFNG • IL12A • NCAM1 • PTPRC

Ankyra Announces Publication of Phase 1 Clinical Data, and Will Present at the Society for Immunotherapy of Cancer (SITC) Annual Meeting (Businesswire) - "The company has an emerging pipeline and will be presenting initial data with their ANK-201 at the Society for Immunotherapy of Cancer annual meeting on November 7, 2025...Exploratory analysis of phase 1 solid tumor patients treated demonstrates baseline levels of circulating natural killer T (NKT) cells may serve as predictive biomarkers of response to anchored IL-12 treatment...Results from an ongoing collaboration with the National Cancer Institute Center for Immuno-Oncology will report on anchored murine IL-12 in combination with a histone deacetylase (HDAC) inhibitor in checkpoint-refractory tumor models."

P1 data • Preclinical • Solid Tumor

ANK-101, an anchored IL-12 drug conjugate, induces immune responses and therapeutic activity in patients with HPV negative squamous cell carcinoma of the head and neck (HNSCC): A subset analysis of the Phase 1 ANCHOR clinical trial [WITHDRAWN] (ESMO 2025) - No abstract available

Clinical • P1 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IL12A

ANK-101-004: A Study of Tolododekin Alfa (ANK-101) in Combination With an Anti-PD-1/PD-L1 Antibody in Participants With Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Ankyra Therapeutics, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Interleukin-12 anchored drug conjugate (tolododekin alfa) in patients with advanced solid tumors: first-in-human Phase 1 trial. (PubMed, Nat Commun) - P1 | "These findings support continued clinical development of tolododekin alfa. ClinicalTrials.gov registration: NCT06171750."

First-in-human • IO biomarker • Journal • P1 data • Oncology • Solid Tumor • CD8 • IL12A • PD-L1

A Study of Tolododekin Alfa (ANK-101) in Renal Allograft Recipients With High Risk Cutaneous Squamous Cell Carcinoma (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Ankyra Therapeutics, Inc

New P1 trial • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Transplantation

ANCHOR: Phase I Study of Tolododekin Alfa (ANK-101) in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=97 | Recruiting | Sponsor: Ankyra Therapeutics, Inc | Trial completion date: Jan 2026 ➔ Jun 2027 | Trial primary completion date: Jul 2025 ➔ Apr 2027

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • IL12A

A Study of Tolododekin Alfa (ANK-101) in Combination With an Anti-PD-1/PD-L1 Antibody in Participants With Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: Ankyra Therapeutics, Inc

New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase 1, open-label, dose expansion cohort of the tolerability of tolododekin alfa (ANK-101) in combination with cemiplimab in cutaneous squamous cell carcinoma. (ASCO 2025) - P1 | "Clinical Trial Registry NCT06171750. Research Sponsor: Ankyra Therapeutics."

Clinical • Combination therapy • IO biomarker • P1 data • Hematological Disorders • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • IL12A

Ankyra Therapeutics Announces Phase 1 Clinical Data at the 2025 AACR Annual Meeting and the first patient has been dosed with tolododekin alfa and cemiplimab (Businesswire) - P1 | N=107 | ANCHOR (NCT06171750) | Sponsor: Ankyra Therapeutics, Inc | "The data was derived from Part 1 of the first-in-human (FIH) ANCHOR Phase 1 clinical trial...Key Study Findings...Primary tumor histology included melanoma (n=7), head and neck cancer (n=4), breast cancer (n=2), bladder cancer (n=1), and apocrine adenocarcinoma (n=1); ANK-101 monotherapy was well-tolerated at doses up to 250 µg/mL with no DLTs or Grade 3 or greater treatment-related treatment-emergent adverse events (TEAEs); Highly efficient tumor retention with low (generally <1%) systemic IL-12-ABP; ANK-101 induced CD8+ T cell recruitment, PD-L1 expression, and inflammatory gene signatures consistent with biologic IL-12 activity.... Ankyra reports that on March 25, 2025 the first patient with advanced cutaneous squamous cell carcinoma was treated with a combination of tolododekin-alfa and Regeneron’s PD-1 inhibitor, Libtayo (cemiplimab), in an expansion cohort to the current Phase 1 trial."

P1 data • Trial status • Bladder Cancer • Breast Cancer • Head and Neck Cancer • Melanoma • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

A pharmacokinetic and pharmacodynamic model of an interleukin-12 (IL-12) anchored-drug conjugate for the treatment of solid tumors. (PubMed, Mol Cancer Ther) - "In addition, serum IFNG may be a surrogate marker for drug activity. The PK modeling predictions may also contribute to determining the optimal clinical dose and schedule of ANK-101 and other anchored drug conjugates in patients with solid tumors."

Journal • PK/PD data • Oncology • Solid Tumor • CD8 • IFNG • IL12A

A phase 1, open-label, dose escalation study of the safety and tolerability of ANK-101 in advanced solid tumors (SITC 2024) - P1 | "Clinical trial information: Clinical Trial Registry NCT06171750. Research Sponsor: Ankyra Therapeutics."

Clinical • IO biomarker • Metastases • P1 data • Oncology • Solid Tumor • CD68 • CD8 • IL12A • PD-L1