MEDI1191 / Moderna - LARVOL DELTA

IL-12 mRNA monotherapy is effective in murine tumors resistant to checkpoint inhibition (SITC 2023) - P1/2 | "MEDI1191 comprises recombinant IL-12 mRNA formulated in lipid nanoparticles for intratumoral (IT) injection resulting in high expression of the cytokine in the immediate tumor microenvironment (TME)...Conclusions Our results support the hypothesis that that IT IL-12 mRNA therapy can beneficially re-profile the TME2 3 and may benefit human cancer patients who have developed resistance to checkpoint inhibitors. 4"

Checkpoint inhibition • IO biomarker • Monotherapy • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • B2M • IL12A

Intratumoral mRNA IL-12 can induce a dose dependent immunostimulatory effect within tumor microenvironment in patients with advanced solid tumors (SITC 2023) - P1 | "1–12 µg MEDI1191 sequentially (Part 1A) or concurrently (Part 1B and Part 1D) with intravenous durvalumab (1500 mg). Conclusions Intratumoral injection of mRNA IL-12 can induce an immunostimulatory effect, including elevated anti-tumor gene signatures and T cell infiltration. Evidence of a dose-dependent immune modulation within the TME was observed at injected lesion sites."

Biomarker • Clinical • IO biomarker • Metastases • Tumor microenvironment • Oncology • Solid Tumor • CD8 • IFNG • IL12A • PD-L1

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=61 | Completed | Sponsor: MedImmune LLC | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Monotherapy • Trial completion • Oncology • Solid Tumor • TNFA

First-in-human study of MEDI1191 (mRNA encoding IL-12) plus durvalumab in patients (pts) with advanced solid tumors (AACR 2022) - P1 | "IT MEDI1191 plus systemic anti-PD-L1 was safe and feasible. Preliminary antitumor efficacy and pharmacodynamics, including tumor CD8+ T cell recruitment, were consistent with expected mechanism of action. Pts with injectable deep visceral and superficial lesions are being recruited."

Clinical • IO biomarker • P1 data • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • IL12A

Intratumoral (IT) MEDI1191 + durvalumab (D): Update on the first-in-human study in advanced solid tumors (AACR 2023) - P1 | "MEDI1191 + D was safe and tolerable in pts with SC/C or deep-seated lesions. Antitumor activity was seen in injected and distant lesions, and pharmacodynamic activity was consistent with expectations based on mechanistic biology."

IO biomarker • Metastases • P1 data • Endocrine Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Melanoma • Neuroendocrine Tumor • Oncology • Sarcoma • Solid Tumor • CD8 • IFNG • IL12A

Intratumoral MEDI1191 encoding IL-12 in solid tumors (YouTube) - "Omid Hamid, MD...provides an overview of the Phase I trial (NCT03946800) assessing MEDI1191, an injectable lipid nanoparticle-formulated therapy containing mRNA encoding IL-12. Whilst there were responses in terms of activation of the immune system, especially in patients with melanoma, the primary endpoint was not met. This interview took place at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, FL."

Interview • Video

MEDI1191 Plus Durvalumab Appears Safe, Active in Advanced Solid Tumors (Cancer Therapy Advisor) - P1 | N=61 | NCT03946800 | Sponsor: MedImmune LLC | "Combination treatment with MEDI1191 and durvalumab has demonstrated activity in certain patients with advanced solid tumors, according to study results presented at the AACR Annual Meeting 2023....The objective response rate was 8.2% overall, 4.0% in part 1A, 14.8% in part 1B, and 0% in part 1D. All responses were partial responses. The median duration of response was not reached (range, 1.9-22.3 months). The disease control rate was 27.9% in the overall cohort, 32.0% for part 1A, and 33.3% for part 1B. None of the patients in part 1D achieved disease control."

P1 data • Oncology • Solid Tumor

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=61 | Active, not recruiting | Sponsor: MedImmune LLC | Recruiting ➔ Active, not recruiting | N=102 ➔ 61 | Trial completion date: Sep 2027 ➔ Aug 2023 | Trial primary completion date: Sep 2027 ➔ Aug 2023

Combination therapy • Enrollment change • Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • TNFA

MEDI1191 (IL-12 mRNA) induces peripheral and intratumoral immunostimulatory effect in patients with cutaneous or subcutaneous (C/SC) lesions (SITC 2022) - P1 | "Methods In an ongoing phase 1 dose escalation study ( NCT03946800 ), patients with C/SC lesions received 0.1-12µg MEDI1191 sequentially (Part 1A) or concurrently (Part 1B) with intravenous durvalumab (1500 mg). There was an associated immunomodulatory effect in the periphery, including elevated IL-12, IFN-γ and activated T-cells. Trial Registration NCT03946800"

Clinical • Oncology • CD8 • CXCL10 • CXCL11 • CXCL9 • GZMB • IFNG • IL12A • IL12RB1 • STAT4

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=102 | Recruiting | Sponsor: MedImmune LLC | Trial completion date: Jan 2027 ➔ Sep 2027 | Trial primary completion date: Jan 2027 ➔ Sep 2027

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • TNFA

[VIRTUAL] MEDI1191, a novel IL-12 mRNA therapy for intratumoral (IT) injection for advanced solid tumours (ESMO 2020) - P1 | "Trial design This phase I, multicenter, open-label, dose-escalation (Part 1) and expansion (Part 2) study (NCT03946800) evaluates the safety and efficacy of MEDI1191 IT in sequential or concurrent combination with durvalumab 1500 mg Q4W IV. Funding: AstraZeneca. Clinical trial identification: NCT03946800."

IO Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IFNG • IL12A

[VIRTUAL] Preliminary safety, antitumor activity and pharmacodynamics results of HIT-IT MEDI1191 (mRNA IL-12) in patients with advanced solid tumors and superficial lesions (TAT 2021) - P1 | "Clinical trial identification NCT03946800. Conclusions Sequential combination of IT MEDI119 with IV durvalumab was well tolerated and showed encouraging preliminary antitumor and pharmacodynamic activity including in IO pre-treated pts, consistent with the expected mechanism of action. The study is active and recruiting."

Clinical • PK/PD data • Melanoma • Oncology • Solid Tumor • CXCL10 • IFNG • IL12A

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors. (clinicaltrials.gov) - P1; N=87; Recruiting; Sponsor: MedImmune LLC; Trial completion date: Oct 2027 ➔ Jan 2027; Trial primary completion date: Oct 2027 ➔ Jan 2027

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • TNFA

Efficacy and safety of MEDI1191 in patients with solid tumors and superficial lesions (YouTube) - "Omid Hamid, MD....presents findings from the Phase I trial (NCT03946800), which evaluated safety and efficacy of MEDI1191 (IL-12 mRNA) in combination with durvalumab in patients with solid tumors. Intratumoral injection of MEDI1191 resulted in localized production of IL-12 in the tumor, stimulating immune cell and IFN gamma production, as well as inducing cytotoxic T cell activity into the tumor area. In the ongoing trial with 10 patients, one patient with head and neck cancer and another with melanoma had a partial clinical response, demonstrating proof of principle."

Video

Safety of continued dosing of MEDI1191 (YouTube) - "Omid Hamid, MD...discusses the safety of continued dosing of MEDI1191 (IL-12 mRNA) during the Phase I trial (NCT03946800), in which patients with solid tumors were intratumorally injected with MEDI1191 in combination with durvalumab. Intratumoral injection of MEDI1191 resulted in localized production of IL-12 in the tumor, stimulating immune cell and IFN gamma production, as well as inducing cytotoxic T cell activity into the tumor area. Despite some toxicity seen in continued dosing, early detection demonstrated the safety of MEDI1191."

Interview • Video

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=87; Not yet recruiting; Sponsor: MedImmune LLC

Clinical • Combination therapy • Monotherapy • New P1 trial • Oncology • Solid Tumor • TNFA

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=87; Recruiting; Sponsor: MedImmune LLC; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Monotherapy • Oncology • Solid Tumor • TNFA

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=87; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Monotherapy • Oncology • Solid Tumor • TNFA

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=79; Recruiting; Sponsor: MedImmune LLC; Trial completion date: Dec 2027 ➔ Nov 2026; Trial primary completion date: Dec 2027 ➔ Nov 2026

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • TNFA

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=79; Recruiting; Sponsor: MedImmune LLC; Trial completion date: Nov 2026 ➔ Sep 2027; Trial primary completion date: Nov 2026 ➔ Sep 2027

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • TNFA

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=87; Recruiting; Sponsor: MedImmune LLC; Active, not recruiting ➔ Recruiting; Trial completion date: Mar 2027 ➔ Dec 2027; Trial primary completion date: Mar 2027 ➔ Dec 2027

Clinical • Combination therapy • Enrollment open • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • TNFA

NCCN: Cancer and COVID-19 Vaccination: Recommendations of the NCCN COVID-19 Vaccination Advisory Committee (NCCN) - "Patients with active cancer and those on treatment should be prioritized for vaccination and should be immunized when any vaccine that has been authorized for use by the FDA is available to them....The committee supports use of any of the available EUA approved vaccines (Pfizer/BioNTech BNT162b2 mRNA vaccine], Moderna [mRNA-1273 SARS-CoV-2 Vaccine] and Janssen/Johnson & Johnson [Ad26.COV2.S Adenovirus vector vaccine]) in patients who are eligible."

NCCN guideline

Prelliminary data with IL-12 mRNA administered by intratumoural injection in combination with intravenous durvalumab (ESMO.org) - P1, N=87; NCT03946800; Sponsor: MedImmune LLC; "These findings were reported at the ESMO Targeted Anticancer Therapies (TAT) Virtual Congress 2021 held on 1-2 March...From May 2019 to December 2020, the study enrolled 10 patients with superficial lesions who were relegated to one of three dose escalation cohorts...In the efficacy analysis, two partial responses (PRs) were demonstrated in patients that had received prior immunotherapy and also had PD-L1 negative tumours. Of these PRs, one occurred in a patient with mucosal melanoma who displayed tumour shrinkage of both injected and non-injected lesions following 2 doses of MEDI1191 that occurred prior to administration of sequential durvalumab."

P1 data • Oncology • Solid Tumor

"mouse data from $MRNA x $AZN hIL-12 mRNA (MEDI1191), but intratumoral admin in the paper" (@BertrandBio)

Preclinical • Oncology

Intratumoral interleukin-12 mRNA therapy promotes TH1 transformation of the tumor microenvironment. (PubMed, Clin Cancer Res) - "These data demonstrate the potential for intratumorally delivered IL-12 mRNA to promote TH1 TME transformation and robust anti-tumor immunity."

Biomarker • IO Biomarker • Journal • Tumor microenvironment • Hepatology • Immune Modulation • Inflammation • Oncology