Ad-CCL21-DC / National Cancer Institute - LARVOL DELTA

HEMONC CIRM IST Lung: CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2025 ➔ Jan 2027 | Trial primary completion date: Jan 2024 ➔ Jan 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Characteristics of a CCL21-gene modified dendritic cell vaccine utilized for a clinical trial in non-small cell lung cancer. (PubMed, Mol Cancer Ther) - "We have embarked on a phase I clinical trial of a vaccine consisting of monocyte-derived DCs (moDCs) modified to express the chemokine CCL21 (CCL21-DC) given in combination with pembrolizumab. A single freeze-thaw cycle for stored vaccines was associated with minor alterations to the DC phenotype, as was the use of healthy donors rather than patient autologous blood. Our results highlight important considerations for the production of DC vaccines and identify underexplored factors that may affect their efficacy and immunologic impact."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL21

Phase I trial of in situ vaccination with autologous CCL21 gene-modified dendritic cells (CCL21-DC) combined with pembrolizumab for metastatic NSCLC (SITC 2024) - P1 | "Conclusions IT CCL21-DC plus pembrolizumab therapy was well tolerated in patients with mNSCLC. No objective responses were observed on trial, but clinical outcomes and correlative analyses suggest enhanced anti-tumor activity resulting from trial therapy."

IO biomarker • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CCL21 • CD8 • EGFR • PD-L1

HEMONC CIRM IST Lung: CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ Jan 2025 | Trial primary completion date: Jun 2024 ➔ Jan 2024

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Phase I trial of intratumoral administration of autologous CCL21 gene-modified dendritic cells in combination with pembrolizumab for advanced NSCLC: Feasibility of repeated IT injections (AACR 2024) - P1 | "Our preclinical studies and phase I trial of intratumoral (IT) administration of DC genetically modified to overexpress CCL21 (CCL21-DC) revealed augmentation of tumor antigen presentation in situ, resulting in systemic antitumor immunity. Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial, NCT03546361, is currently open for enrollment, and this updated abstract will highlight the feasibility of repeated IT injections in treated patients."

Combination therapy • IO biomarker • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CCL21 • EGFR • PD-L1

CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity. (PubMed, J Immunother Cancer) - "CCL21-DC ISV synergizes with anti-PD-1 to eradicate murine NSCLC. Our data support the clinical application of CCL21-DC ISV in combination with checkpoint inhibition for patients with NSCLC."

IO biomarker • Journal • Preclinical • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL21 • CD4 • CD8 • KRAS • STK11 • TMB • TP53

HEMONC CIRM IST Lung: CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL21 • CD4 • CD8 • PD-1 • PD-L1

Vaccine Therapy in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1; N=17; Completed; Sponsor: Jonsson Comprehensive Cancer Center; Active, not recruiting ➔ Completed; Trial completion date: Feb 2019 ➔ May 2017; Trial primary completion date: Feb 2018 ➔ May 2017

Trial completion • Trial completion date • Trial primary completion date • Biosimilar • Immune Modulation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase I trial of in situ vaccination with autologous CCL21-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced NSCLC. (ASCO 2022) - P1 | "Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial is currently open for enrollment."

IO biomarker • P1 data • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CCL21 • EGFR • PD-L1

Phase I trial of in situ vaccination with autologous CCL21 gene-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced non-small cell lung cancer (NSCLC) (AACR 2022) - P1 | "Secondary objectives include adverse event profiling and immune monitoring studies.[B.L. and A.L. contributed equally to this work as first authors.]"

IO biomarker • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CCL21 • EGFR

Phase I trial of in situ vaccination with autologous CCL21-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced NSCLC (ESMO 2022) - P1 | "Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial, NCT03546361, is currently open for enrollment."

IO biomarker • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CCL21 • EGFR • PD-L1

Tumor Vaccination with Cytokine-Secreting Dendritic Cells Sensitizes Murine NSCLC to Anti-PD-1 Therapy (ATS 2022) - "In preclinical studies as well as a phase I clinical trial, we have discovered that intratumoral (IT) vaccination with gene-modified dendritic cells expressing CCL21 (CCL21-DC) promotes effector T lymphocyte infiltration into the tumor, PD-L1 upregulation, and systemic tumor-specific immune responses...Tumor vaccination with IT DC-CCL21 sensitizes immune-resistant murine NSCLC to anti-PD-1 therapy. Combination therapy enhances anti-tumor T cell responses, resulting in immunoediting of tumor subclones and the generation of systemic tumor-specific immunity."

IO biomarker • Preclinical • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL21 • CD8 • ITGAE • KRAS • STK11 • TMB

In situ vaccination with CCL21-DC sensitizes non-responsive murine NSCLCs to anti-PD-1 therapy and generates systemic tumor-specific immune memory (AACR 2022) - "Combination therapy enhances anti-tumor T cell responses, resulting in immunoediting of tumor subclones and the generation of systemic tumor-specific immunity. In an ongoing clinical trial, we are evaluating the safety and efficacy of ISV with CCL21-DC in combination with anti-PD-1, pembrolizumab, in patients with advanced NSCLC who have progressed on front-line therapy."

IO biomarker • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL21 • CD8 • ITGAE • KRAS • STK11 • TMB

[VIRTUAL] Phase I Trial of in Situ Vaccination With Autologous CCL21 - Modified Dendritic Cells (CCL21 - DC) Combined With Pembrolizumab for Advanced NSCLC (IASLC-WCLC 2021) - P1 | "Our preclinical studies and phase I trial of intratumoral (IT) administration of DC genetically modified to overexpress CCL21 (CCL21-DC) revealed augmentation of tumor antigen presentation in situ, resulting in effective T cell responses and systemic antitumor immunity. Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial, NCT03546361, is currently open for enrollment."

IO biomarker • P1 data • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CCL21 • EGFR • PD-L1

[VIRTUAL] Phase I trial of in situ vaccination with autologous CCL21-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced NSCLC. (ASCO 2021) - P1 | "Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies . This trial, NCT03546361, is currently open for enrollment."

IO biomarker • P1 data • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CCL21 • EGFR • PD-L1

HEMONC CIRM IST Lung: CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Jonsson Comprehensive Cancer Center; Trial completion date: Jun 2023 ➔ Jun 2024; Trial primary completion date: Jun 2022 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL21 • CD4 • CD8 • PD-1 • PD-L1

HEMONC CIRM IST Lung: CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Jonsson Comprehensive Cancer Center; N=36 ➔ 24; Trial completion date: Nov 2023 ➔ Jun 2023; Trial primary completion date: Nov 2022 ➔ Jun 2022

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL21 • CD4 • CD8 • PD-1 • PD-L1

VTNSCLC: A Vaccine Trial for Patients With Stage IIIB, IV, or Recurrent Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1; N=1; Terminated; Sponsor: VA Office of Research and Development; N=16 ➔ 1

Enrollment change • Biosimilar • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Adenovirus CCL-21 Transduced MART-1/gp100/Tyrosinase/NY-ESO-1 Peptide-Pulsed Dendritic Cells Matured (clinicaltrials.gov) - P1; N=13; Completed; Sponsor: H. Lee Moffitt Cancer Center and Research Institute; Active, not recruiting ➔ Completed

Clinical • Trial completion

Adenovirus CCL-21 Transduced MART-1/gp100/Tyrosinase/NY-ESO-1 Peptide-Pulsed Dendritic Cells Matured (clinicaltrials.gov) - P1; N=13; Completed; Sponsor: H. Lee Moffitt Cancer Center and Research Institute; N=18 ➔ 13

Clinical • Enrollment change

HEMONC CIRM IST Lung: Intratumoral Administration of CCL21-gene Modified Dendritic Cell With Intravenous Pembrolizumab for Advanced NSCLC (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Jonsson Comprehensive Cancer Center; Not yet recruiting ➔ Recruiting

Enrollment open