Immune System Diseases

All Conditions

Neoplasms

Blood and Lymph Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Hypersensitivity

Sarcoma

Lymphoma

Adenocarcinoma

Melanoma

Head and Neck Neoplasms

Soft Tissue Sarcoma

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

HNSCC patients presenting with a surface accessible lesion who are scheduled for tumor and/or regional node dissection as part of their standard treatment will be injected one to three days prior to surgery using the CIVO device. The planned injection scheme includes: vehicle control and microdoses of rilvegostomig, volrustomig, sabestomig, and pembrolizumab alone.

Intratumoral microdose injection by the CIVO device.

Rilvegostomig

Volrustomig

Sabestomig

Presage Biosciences

Randev Clinical Research Supervisor

Arnaud Bewley, MD

Allyson Anderson

Mihir Patel, MD

Ken Cardona, MD

Research Coordinator

Sid Sheth, MD

Jeffrey Houlton, MD

Ernest Conrad, MD

Roxanne Moore

Elyse Brinkmann, MD

Study Director

This is a multi-center, open-label Phase 0 Master Protocol designed to study the localized pharmacodynamics (PD) of anti-cancer therapies within the tumor microenvironment (TME) when administered intratumorally in microdose quantities via the CIVO device in patients with surface accessible solid tumors for which there is a scheduled surgical intervention. CIVO stands for Comparative In Vivo Oncology. Multiple substudies will include specified investigational agents and combinations to be evaluated.

CIVO is a research tool composed of a hand-held single-use sterile injector coupled with fluorescent tracking microspheres called CIVO GLO that mark the sites of drug microdose injection, enabling rapid assessment of multiple oncology drugs or drug combinations simultaneously within a patient's tumor. Tumor responses to cancer treatments are highly context-specific and often involve complex interactions between the anti-cancer therapy, genetically diverse tumor cells, and a heterogeneous TME. This complexity is rarely modeled accurately in preclinical translational models of cancer. By utilizing intratumoral microdose injections with CIVO in advance of scheduled surgical intervention, this study will evaluate anti-cancer therapies directly in patients each with their own unique tumor genomic profile, intact TME, and immune system functional status. Because the platform delivers microdose amounts of each test agent or combination directly into the patient's tumor tissue, hypotheses can be tested earlier in the drug development process, consistent with the goals of the 2006 FDA Exploratory IND Guidance for Industry.

The CIVO device penetrates solid tumors and simultaneously delivers subtherapeutic microdoses of up to eight anti-cancer agents or combinations of anti-cancer agents co-injected with CIVO GLO into discrete regions of the tumor as drug columns. At the time of the planned surgical intervention (at least four hours to up to seven days after the CIVO microdose injection), the injected tumor tissue is then excised and tumor responses are assessed via histological staining of tumor cross-sections sampled perpendicular to each injection column. Co-injection with CIVO GLO enables identification of each injection site during resection as well as in tissues stained for analysis. This Phase 0 Master Protocol is aimed at distinguishing promising candidates earlier in the drug development process while also avoiding systemic toxicities associated with typical clinical exposures to these therapies.

This Master Protocol is designed as an umbrella concept trial for the ongoing evaluation of multiple agents in individual CIVO Phase 0 substudies. Based on regulatory guidance on Phase 0 clinical trial design, approximately up to 15 participants are planned to be enrolled in each substudy in order to complete with approximately up to 12 evaluable tumor samples. Each substudy is considered an "Experimental Arm" with specified tumor types, inclusion and exclusion criteria, and investigational agents and combinations to be evaluated. Tumor type examples accessible for CIVO injection include, but may not be limited to, Head and Neck Cancer, Melanoma, Soft Tissue Sarcoma, Breast Cancer, or Lymphoma. Comparisons will not be made between experimental arms/substudies.

The following substudy(ies) is(are) currently active:

- MST01-AZN-05 (NCT06366451) evaluating rilvegostomig, volrustomig, sabestomig, and pembrolizumab.

New substudies will be continuously added as they become active.

Phase 0 Master Protocol for CIVO Intratumoral Microdosing of Anti-Cancer Therapies

A Phase 0 Master Protocol Using the CIVO® Platform to Evaluate Intratumoral Microdoses of Anti-Cancer Therapies in Patients With Solid Tumors

Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumor microenvironment around each of the injection sites in each resected patient sample by IHC, ISH, or spatial biology platforms. An aggregate analysis of this quantification may be done across patient samples in each substudy to evaluate trends in tumor response. The biomarkers evaluated may include, but are not limited to biomarkers for cell death (e.g. cleaved caspase 3), T-cells (e.g. CD3, CD8/Granzyme B, CD4), natural killer (NK)/myeloid cells (e.g. CD56/Granzyme B, CD86, CD68, CD163), and proinflammatory cytokines (e.g., interferon gamma, tumor necrosis factor alpha, interferon gamma-induced protein 10).

Relationship of AE to study drug(s) or CIVO device will be determined using an AE Relatedness Grading System.

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Analgesics

Central Nervous System Depressants

Morphine

Clinical Research Supervisor

This is a multi-center, open-label, Phase 0 substudy designed to evaluate the localized pharmacodynamics (PD) of rilvegostomig, volrustomig, and sabestomig within the tumor microenvironment (TME) when administered intratumorally in microdose quantities via the CIVO device in patients presenting with Head and Neck Squamous Cell Carcinoma (HNSCC) with a surface accessible lesion, who are scheduled for tumor and/or regional node dissection as part of their standard treatment. PD effects due to injected investigational agents will be compared to those elicited by pembrolizumab alone, which will also be injected in microdose quantities via the CIVO device.

The CIVO Microdose Injection Device (MID) simultaneously delivers multiple drugs and drug combinations (Up to 8), each in microdose amounts, into a single patient tumor and enables comparisons of the resulting biomarker responses that occurred while that tumor was still in the native microenvironment. AstraZeneca is developing three novel assets: rilvegostomig, volrustomig, and sabestomig, all of which are bispecific monoclonal antibodies designed to stimulate antitumor immunity. In this Phase 0 clinical trial, the PD effects of these investigational assets in the TME of patients presenting with HNSCC will be evaluated. These investigational assets will be injected alone in microdose quantities at tumor sites in HNSCC patients. Pembrolizumab, also used therapeutically in this patient population, will be included in the CIVO injection array administered as a single agent. The CIVO-injected portion of the tissue will be analyzed for localized response at sites of drug exposure in the TME.

This is an exploratory clinical trial to evaluate intratumoral mechanistic effects of novel and approved agents on intact human tumors. This is a cohort substudy of a Master Protocol (PBI-MST-01, NCT04541108) framework, under which comparisons will not be made between substudy cohorts.

PBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, and Sabestomig in HNSCC

A Phase 0 Multicenter Study of the Pharmacodynamic Effects of Intratumoral Microdose Administration of Rilvegostomig, Volrustomig, and Sabestomig

The localized activity of injected microdoses will be analyzed using the NanoString GeoMx Digital Spatial Profiler (DSP) and the GeoMx Cancer Transcriptome Atlas to comprehensively profile over 1800 genes simultaneously with spatial resolution to describe tumor biology, the TME, and the immune response signatures of each drug at an injection site. DSP outcomes may be validated via IHC or ISH technique.

Safety of the microdose injection procedure and injected content will be assessed by quantification of the frequency, intensity, and relatedness of all reported Adverse Events and/or Adverse Device Effects.

AstraZeneca

Spots Global Cancer Trial Database for sabestomig

Every month we try and update this database with for sabestomig cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 0 Master Protocol for CIVO Intratumoral Microdosing of Anti-Cancer Therapies	NCT04541108	Solid Tumor	Rilvegostomig Volrustomig Sabestomig Pembrolizumab	18 Years -	Presage Biosciences
PBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, and Sabestomig in HNSCC	NCT06366451	Head and Neck S...	Rilvegostomig Volrustomig Sabestomig Pembrolizumab	18 Years -	Presage Biosciences
Phase 0 Master Protocol for CIVO Intratumoral Microdosing of Anti-Cancer Therapies	NCT04541108	Solid Tumor	Rilvegostomig Volrustomig Sabestomig Pembrolizumab	18 Years -	Presage Biosciences
Phase 0 Master Protocol for CIVO Intratumoral Microdosing of Anti-Cancer Therapies	NCT04541108	Solid Tumor	Rilvegostomig Volrustomig Sabestomig Pembrolizumab	18 Years -	Presage Biosciences

Spots Global Cancer Trial Database for sabestomig

Every month we try and update this database with for sabestomig cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for sabestomig cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.