Bispecific Personalized Aptamer for intratumoral administration

AM003

Irit Carmi Levy, PhD

Leanne Amitzi, PhD

Inbar Kolsky

Ruth Perets, MD

Nechama Busheri

Aron Popovtzer, MD

Chen Meir

Salomon Stemmer, Prof.

Ilanit Redinsky

Eytan Ben Ami, MD

Yasmin Levi

Ravit Geva, MD

This is a phase 1, first-in-human study to assess the safety and tolerability of AM003 in patients with locally advanced and metastatic solid tumors

This is a phase 1, open-label , multicenter dose escalation trial evaluating the safety and tolerability of AM003 , administered intratumorally to patients with locally advanced and metastatic solid tumors

Study of AM003 in Patients With Locally Advanced and Metastatic Solid Tumors

A Phase I, Open-Label Multicenter Study of AM003 Dose Escalation, Administered Intratumorally to Patients With Locally Advanced and Metastatic Solid Tumors

Number and percent of participants experiencing dose-limiting toxicities (DLTs), Grade 3 non-hematological adverse AEs, Grade 4 hematological AEs, and discontinuations of study drug due to AE intolerance.

Estimating the ORR, Disease Control Rate, CR, PR and SD lasting at least 8 weeks by RECIST 1.1

Estimating the ORR, Disease Control Rate, CR, PR and SD lasting at least 8 weeks by iRECIST.

Aummune Ltd.

Neoplasms

All Conditions

Digestive System Diseases

Immune System Diseases

Rare Diseases

Carcinoma

Stomach Neoplasms

Hypersensitivity

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Patients with stage III gastric cancer who need neoadjuvant chemotherapy before radical surgery are recruited. And they are treated with individualized neoadjuvant therapy under the guidance of a patient-derived organoid (PDO)-based drug sensitivity assay.

Patients with stage III gastric cancer who need neoadjuvant chemotherapy before radical surgery are recruited. In this group, patients are treated with the SOX regimen.

PDO group

Traditional group

Jin Sun, PhD

Yanye Yang, Bachelor

Jing Sun, PhD

Neoadjuvant chemotherapy has become the mainstream recommended treatment for advanced gastric cancer. However, due to the heterogeneity of gastric cancer, part of some patients fail to benefit from the treatment. This project aims to compare the clinical efficacy of individualized neoadjuvant therapy based on patient-derived organoid drug sensitivity assay and traditional regimen, exploring the advantages and disadvantages of these two treatments. And access the safety and clinical value of the personalized neoadjuvant therapy based on patient-derived organoid drug sensitivity assay in advanced gastric cancer.

The Clinical Efficacy of Drug Sensitive Neoadjuvant Chemotherapy Based on Organoid Versus Traditional Neoadjuvant Chemotherapy in Advanced Gastric Cancer

The Clinical Efficacy of Patient-derived Organoid-based Drug Sensitive Neoadjuvant Chemotherapy Versus Traditional Neoadjuvant Chemotherapy in Advanced Gastric Cancer: a Prospective Multi-center Randomized Controlled Study

proportion of patients whose tumor volume reduced to a predetermined value and maintain the minimum time limit.

grade the pathological response of tumor after neoadjuvant treatment, which is usually classified according to the proportion of fibrosis and residual tumor in tumor tissues.

proportion of patients who relapse within 3 years after operation

Wuxi Branch of Ruijin Hospital

Shanghai OneTar Biomedicine Co., Ltd.

Shanghai Minimally Invasive Surgery Center

Symptoms and General Pathology

Recurrence

Glioblastoma

Disease Attributes

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Patients will be treated with drugs based on functional profiling of autologous tumor cells in vitro

A personalized drug combination will be prescribed to each patient based on the functional drug screen

Personalized drug combination

Einar O. Vik-Mo, MD, PhD

Erlend Skaga, MD, PhD

Einar O Vik-Mo, MD, PhD

Solveig Bringsli

Petter Brandal, MD, PhD

A study to determine the feasibility and safety of individualized cancer stem cell targeted therapy based on high-throughput functional profiling of FDA/EMA-approved drugs in patients with GBM that has recurred or progressed following standards-of-care (RT, TMZ).

This protocol describes a prospective single-center phase 1 study to evaluate the feasibility and safety of a high-throughput drug sensitivity and resistance testing (HTS) platform of individualized cancer stem cells (CSC) to predict targeted therapies in patients with recurrence of GBM after standards-of-care. Secondary outcome include efficacy of drug treatment. The underlying hypotheses is that treatment of patients based on functional profiling og autologous CSCs using HTS a) is feasible within an acceptable time window for clinical translation, b) safely delay disease progression and c) increase survival. There are increasingly published literature that strongly support the importance of a targeting CSC to improve therapy and prevent tumor recurrence in GBM, as an additional strategy to improve the overall prognosis of patients.

Individualized Systems Medicine Functional Profiling for Recurrent Glioblastoma

Individualized Systems Medicine Strategy for Targeting Cancer Stem Cells in Patients With Recurrent Glioblastoma (ISM-GBM)

Anonymized data will regarding tumor characteristics and results of functional profiling will be made available after publishing.

The fraction of patient that can receive an individualized treatment based on drug screening. These drugs must be available for treatment and with a combined acceptable toxicity.

Tumor response by the chosen drug combination evaluated according to the updated response assessment in neuro-oncology (RANO) criteria.

Adverse events induced by selected treatments according to NCI Common Terminology Criteria for Adverse Events.

Overall survival in treated patients from time of second surgery to all-cause mortality.

Evaluated by Eastern Cooperative Oncology Group Quality of Life Questionaire (QLQ-C30), a questionnaire developed to assess the quality of life of cancer patients. Scale 30 to 120 points, where higher is worse.

Evaluated by Eastern Cooperative Oncology Group Quality of Life Questionaire, Brain module (QLQ-BN20). The brain cancer module is meant for use among brain cancer patients varying in disease stage and treatment modality. Scale 20 to 80 points, where higher is worse.

Institute for Molecular Medicine

Oslo University Hospital

Head of Surgical Neuro-Oncology

Antineoplastic Agents

All Drugs and Chemicals

Decitabine

Arsenic Trioxide

Antimetabolites

Enzyme Inhibitors

decitabine: 20mg/m2/d, intravenously, d1-d5, q4w arsenic trioxide: 0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d)

0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d)

Min Lu, PhD

Sujiang Zhang, MD, PhD

Sujiang Zhang, PhD

TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. Here the investigators try to evaluate the side effect and treatment potential of DAC+ATO in p53 mutated high-risk AML/MDS patients.

About 200 AML/MDS patients will be sequenced for TP53 sequence before recruitment. The investigators estimated about 5 patients, based on the reported p53 mutation frequency in AML/MDS, will be p53-mutated. In the trial, the investigators will selectively recruit the mp53 AML/MDS patients that are predicted to respond to DAC+ATO regimen with highest chance (based on the relevant basic studies).

The investigators designate mutant p53-based clinical trials as 'PANDA (P53 AND Arsenic)-Trials'.

TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. In two independent clinical trials reported recently, DNA demethylating drug Decitabine (DAC) treatment yielded a surprisingly high rate of complete remission (CR) in mp53-expressing myelodysplastic syndromes (MDS) patients and acute myeloid leukemia (AML) patients. Notably, all of the mp53-expressing patients in the two clinical studies, despite of CR, relapsed quickly. This was attributed to a failure in thoroughly clearing all leukemia-specific mutations and the preexisting mp53 subclone outgrew in all of the relapse patients. Indeed, The investigators also found p53 dysfunctional cells quickly develop a DAC resistance mechanism in cultured tissue (unpublished data). Meanwhile, the investigators found arsenic trioxide (ATO) selectively inhibit p53-mutated cells involving mutant p53 reactivation and mutant p53 degradation (presumably mediated by upregulated mdm2 and RCHY1/Pirh2 through reactivated mutant p53). In addition, DAC and ATO show synergy in inhibiting p53-mutated cells.

In current phase I trial, the investigators try to evaluate the side effect and treatment potential of DAC+ATO in p53 mutated high-risk MDS patients. About 200 AML/MDS patients will be recruited for TP53 sequencing before being trialed. The investigators estimated about 50 patients, based on p53 mutation frequency in AML/MDS, will be sequenced to be mp53-positive. The mp53-positive AML/MDS patients are known to have an extremely poor prognosis. The investigators will select high-risk mp53 MDS patients that are predicted to respond to DAC+ATO with highest chance based on our relevant basic studies.

The other participants (free of p53 mutation) will be excluded from the trial.

Mutant p53-based Personalized Trial Using Decitabine and Arsenic Trioxide on AML/MDS

Combination of Decitabine and ATO to Treat AML/MDS Expressing a Classified Type of Mutant p53

evaluate the side effects of current regimen

Partial response (PR) + complete response (CR) rate

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of AM003 in Patients With Locally Advanced and Metastatic Solid Tumors	NCT06258330	Solid Tumor	AM003	18 Years -	Aummune Ltd.
The Clinical Efficacy of Drug Sensitive Neoadjuvant Chemotherapy Based on Organoid Versus Traditional Neoadjuvant Chemotherapy in Advanced Gastric Cancer	NCT05351398	Advanced Gastri...	PDO group Traditional gro...	18 Years - 80 Years	Shanghai Minimally Invasive Surgery Center
Individualized Systems Medicine Functional Profiling for Recurrent Glioblastoma	NCT05043701	Recurrent Gliob...	Personalized dr...	18 Years - 70 Years	Oslo University Hospital
Individualized Systems Medicine Functional Profiling for Recurrent Glioblastoma	NCT05043701	Recurrent Gliob...	Personalized dr...	18 Years - 70 Years	Oslo University Hospital
Mutant p53-based Personalized Trial Using Decitabine and Arsenic Trioxide on AML/MDS	NCT03855371	P53 Mutation Myeloid Maligna... MDS Aml	Decitabine Arsenic Trioxid...	18 Years - 75 Years	Ruijin Hospital

Spots Global Cancer Trial Database for personalized treatment