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.

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Infections

Symptoms and General Pathology

Digestive System Diseases

Diabetes Mellitus

Communicable Diseases

End Stage Liver Disease

Liver Diseases

Gastrointestinal Diseases

Liver Failure

Hepatic Insufficiency

Anti-Inflammatory Agents

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

Hematinics

Tacrolimus

Triamcinolone

Triamcinolone Acetonide

Triamcinolone hexacetonide

Triamcinolone diacetate

Cyclosporine

Cyclosporins

Liver Extracts

Mitogens

Calcineurin Inhibitors

This is set as reference a cohort of untreated healthy volunteers, over which will be measured the biomarkers to determine the baseline. Implies PBMC ex-vivo exposure to Tacrolimus prior all cell incubations to study ex-vivo PD in stimulated conditions with mitogens to identify potential genetic sources of interindividual variability in physiological conditions Number proposed 30.

To explore PD/PG/PK relationships of TAC residual PD activities ex-vivo in stimulated and non-stimulated conditions in liver recipients.

The number proposed is 50.

To study the ex-vivo PD response to TAC in stimulated and non-stimulated conditions and the potential genetic sources of PD variability in pathological conditions.

The number proposed is 12.

To explore PD/PG/PK relationships of CsA residual PD activities ex-vivo in stimulated and non-stimulated conditions in liver recipients.

The number proposed is 10.

Patients form the waiting list for liver transplantation will be enrolled and monitored at different times after transplantation to study the relationships between TAC PD and the clinical responses.

The number proposed is 20.

Ofelia M Noceti, PhD, PharmD

Solange Gerona, MD

To search for suitable pharmacodynamic biomarkers, i.e., with high specificity for calcineurin inhibition and most affected by inter-individual variability, our works aimed at exploring the pharmacodynamics of CNI, the strength and variability of signal translation along the calcineurin pathway, as well as the steps where sources of internal (genetic) or external variability are the most influential.

In order to achieve this, we assessed simultaneously NFAT1 translocation into the nucleus of peripheral blood mononuclear cells (PBMC) (NFTA1 being the main NAFT isoform in resting and activated lymphocytes), the intracellular expression of IL-2 in CD3+, CD4+ and CD8+ T cell subsets and the membrane expression of CD25 (IL-2Rα), a surface marker of T cells activation, in T cells at large. A non-interventional clinical trial was set up in healthy volunteers, patients registered on a liver transplantation waiting list (WLP) and liver transplant recipients (LTR). A different question was addressed in each group: The healthy volunteer study (n=35): explored TAC PD along the calcineurin pathway by exposing PBMC ex-vivo; modelled signal translation along this cascade; examined the interindividual variability of TAC PD parameters; and investigated the sources of the variability observed and their contribution at each step of the calcineurin pathway. Furthermore, it allowed us to evaluate the analytical variability of our techniques as well as the intra-individual variability of TAC PD parameters. WLP (n=19) were enrolled to confirm in patients with liver diseases the results obtained in healthy volunteers, as well as to test the potential influence of their initial disease on the ex-vivo pharmacodynamics of TAC. The aims of the transversal study of LTR on CNI (n=80) were to further explore the interindividual variability in the PD of CNI in realistic clinical conditions, i.e. in situations of residual PD activities under tacrolimus or cyclosporine exposure, and the potential pharmacogenetic (PG) sources of such variability. The (still small) group of liver transplant patients (n=9) enrolled immediately before transplantation and followed-up with serial monitoring along the first year post-transplantation was intended to explore the relationships between CNI PD and clinical responses.

The research will be conducted under the rules of Good Clinical Practice, Good Laboratory Practice of the International Conference on Harmonisation (ICH)and the Principles of Declaration of Helsinki.

Groups of study are included once inclusion/exclusion criteria were verified and after written informed consent was given: healthy volunteers, patients of the waiting list for liver transplantation, liver transplant recipients on tacrolimus and cyclosporine and a longitudinal cohort of patients enrolled since the waiting list for transplantation.

From this instance proceed the sampling plan. Considering potential dropouts or withdrawals during the study, the intention is to recruit an additional 10% to compensate for the cohorts, as they allow.

The study design does not suppose applying masking methods, since it is an open study.

All data required in the registration forms will be recorded, however in case of persistent failure, will be properly documented the reasons for the absence. Each instance will merit a particular analysis, dated and signed.

Models could be used to estimate the impact of bias due to potential missing data, and if applicable will be complemented with a sensibility analysis.

Loading data will be conducted electronically. Data will be validated according to the data management plan, jointly defined by the principal investigator and the biostatistician, including freezing and thawing processes.

Pharmacokinetic, pharmacogenetic and pharmacodynamic modeling will be done using R software.

Data back ups will be run everyday, and will be archived on tape and a USB storage drive.

Besides self monitoring procedures, the study may be audited by the health authority (during the course of the study or even when it is completed), to assess compliance with the standards of Good Clinical Practice.

Atypical results if any, will be handled according to the criteria of results outside of specification. If re-analysis of samples will occur, they will be properly documented.

Sample size calculation includes the percentage of occurrence of acute cellular rejection and adverse events, as reported by the National Liver Transplant Program and the possible rates of abandonment or premature retirement of the in study subjects.

Under national rates, will be studied at least 30 healthy volunteers, 50 patients and 12 patients with end stage liver disease enlisted for liver transplantation, with serial follow-up during the first year.

Statistical analysis will be performed according to the principle of "intention to treat", and will be the responsible for at least one specialist in biostatistics.

It will be developed a descriptive analysis of all variables collected. Categorical variables will be expressed in percentages and number of observations. Continuous variables will be expressed as mean and coefficient of variation or median and 25th and 75th percentiles, minimum and maximum. Lof transformations will be held whenever needed.

The variables will be compared between groups according to the patient's original listing (intention to treat). They will be calculated and presented the estimated relative risks and their effect with 95% confidence intervals.

For comparison of categorical variables, it will be used the Chi-square test or Fisher's exact test as appropriate.

For comparison of continuous variables, it will be used the test "t" of Student.

For variables that develop with time, they will be represented by Kaplan-Meier curves and compared using the "log-rank" test. Their relative risk with 95% confidence interval will be calculated.

To identify variables associated with different responses multivariate linear analysis, logistic or Cox proportional will be used.

All analyzes will be performed with hypothesis testing and a 2-tailed significance level of 5%.

The program used will be R. Multivariate analysis will be held corrected according Bonferroni's criteria.

We have established standard operating procedures to describe blood collection instances, biological fluids sampling circuit, evaluation of the candidates to include in the study, verification of the inclusion criteria, monitoring of patients during the study, record of undesirable events and report of adverse drug reactions, terminating tracking.

Study of PD/PK/PG Relationships of Tacrolimus and Cyclosporin in Liver Transplant Patients

Study of Pharmacodynamic, Pharmacokinetic and Pharmacogenetic Relationships of Anticalcineurin Drugs: Tacrolimus and Cyclosporin in Liver Transplant Recipients.

Through scientific publications and congresses

Related to the influence of genetic variants in anticalcineurin drug pharmacodynamics

Related to whole blood target calcineurin inhibitor concentration values

Related to calcineruin activation/inhibition (enzyme target of this group of drugs).

Related to T cell function and the maintenance of T cell response.

Recipients's Immune response to his graft

INSERM UMR-S850, Limoges, France

University Hospital, Limoges

PEDECIBA, Uruguay

Universidad de la Republica

ANII (Agencia Nacional de Investigación e Innovación), Uruguay

Scientific Cooperation Service, French Embassy, Uruguay

Hospital Central de las Fuerzas Armadas, Uruguay

ECOS Sud Program France-Uruguay

National Center for Liver Transplantation, Uruguay

UDA Centro Nacional Hepato-Bilio-Pancreático

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

Pharmaceutical Solutions

Nivolumab

Patients with HNSCC who are scheduled for surgical biopsy or tumour resection surgery will be injected at least four hours to up to three days prior to surgery using the CIVO device. Each needle of the CIVO device will deliver up to 8.3 microliters of solution, including a vehicle control (sterile saline and solution stabilizer), a pre-cleaved/pre-activated drug control (cMVC-101), MVC-101 (the prodrug), or nivolumab as single agents or as combinations. Each drug will be delivered in subtherapeutic microdoses, and each microdose is simultaneously injected in a columnar fashion through each of 3, 5, or 8 needles (in a device configuration determined by tumour dimensions) into a single solid tumour or effaced metastatic lymph node.

Intratumoural microdose injection by the CIVO device.

MVC-101

MVC-101 + Nivolumab

Medical Director

This is a multi-center, open-label Phase 0 Master Protocol in Australia designed to study the localized pharmacodynamics (PD) of anti-cancer therapies within the tumour microenvironment (TME) when administered intratumourally in microdose quantities via the CIVO device in patients with surface accessible solid tumours 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 tumour. Tumour responses to cancer treatments are highly context-specific and often involve complex interactions between the anti-cancer therapy, genetically diverse tumour cells, and a heterogeneous TME. This complexity is rarely modeled accurately in preclinical translational models of cancer. By utilizing intratumoural 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 tumour 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 tumour tissue, hypotheses can be tested earlier in the drug development process.

The CIVO device penetrates solid tumours 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 tumour 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 tumour tissue is then excised and tumour responses are assessed via histological staining of tumour 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. Each substudy is considered an "Experimental Arm" with specified investigational agents and combinations to be evaluated. Comparisons will not be made between experimental arms.

CIVO Intratumoural Microdosing of Anti-Cancer Therapies in Australia

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

Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumour microenvironment around each of the injection sites in each resected patient sample by IHC and ISH. An aggregate analysis of this quantification may be done across patient samples in each substudy to evaluate trends in tumour 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, tumour necrosis factor alpha, interferon gamma-induced protein 10).

Takeda

Paclitaxel

Carboplatin

Fluorouracil

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected at least four hours to up to four days prior to surgery using the CIVO device. Each needle of the CIVO device will deliver up to 8.3 microliters of solution, including a vehicle control (sterile saline) or subtherapeutic microdoses of TAK-676, carboplatin, 5-fluorouracil (5- FU), or paclitaxel as single agents or in combination. Each microdose is simultaneously injected in a columnar fashion through each of 8, 5, or 3 needles (in a device configuration determined by tumor dimensions) into a single solid tumor or effaced metastatic lymph node.

TAK-676

5-FU

TAK-676 + Carboplatin

Carboplatin + Paclitaxel

Carboplatin + 5-FU

TAK-676 + Carboplatin + 5-FU

TAK-676 + Carboplatin + Paclitaxel

Wendy Jenkins

This is a multi-center, open-label Phase 0 substudy designed to study the localized pharmacodynamics (PD) of TAK-676 alone or in combination with Carboplatin, 5-FU, or Paclitaxel within the tumor microenvironment (TME) when administered intratumorally in microdose quantities via the CIVO device in patients diagnosed with Head and Neck Squamous Cell Carcinoma presenting with a surface accessible solid tumor for which there is a scheduled surgical intervention. This substudy is a cohort of the PBI-MST-01 Master Protocol.

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.

In this Phase 0 intratumoral microdosing substudy in human patients with Head and Neck Squamous Cell Carcinoma (who will be undergoing previously planned tumor and/or regional node dissection), we will evaluate the ability of TAK-676 to activate innate immune effector cells within the local tumor microenvironment. Additionally, this study will examine the effect of TAK-676 in combination with Carboplatin, or Paclitaxel, or in combination with 2 agents Carboplatin and 5-FU, or Carboplatin and Paclitaxel to study whether TAK-676 enhances the localized immune responses compared to both immunotherapy combinations or Carboplatin alone. All investigational drug combinations will be delivered intratumorally in subtherapeutic microdose quantities via the CIVO platform.

The CIVO Microdose Injection Device (MID) penetrates solid tumors and 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. At the time of the planned surgical intervention (4 hours up to four 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 biomarker analysis. Because the platform delivers microdose amounts of each test agent, or combination, directly into the patient's tumor tissue, mechanistic hypotheses can be tested early in the drug development process, consistent with the goals of the 2006 FDA Exploratory Investigational New Drug (IND) Guidance for Industry.

This is an exploratory clinical trial to evaluate intratumoral mechanistic effects of novel and approved agents on intact human tumors. This substudy is not blinded. This is a cohort substudy of a Master Protocol (PBI-MST-01, NCT 04541108) framework that describes the experimental workflow for use of the CIVO platform. Comparisons will not be made between substudy cohorts.

PBI-MST-01(NCT04541108) Substudy TAK-02: Intratumoral Microdosing of TAK-676 in HNSCC

TAK-676 Alone and in Combination(s) With Carboplatin, 5-Fluorouracil, and Paclitaxel in Patients With Head and Neck Squamous Cell Carcinoma

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 and ISH. 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., Cluster of Differentiation 3 (CD3), Cluster of Differentiation 8/Granzyme B, Cluster of Differentiation), natural killer (NK)/myeloid cells (e.g., Cluster of Differentiation 56/Granzyme B, Cluster of Differentiation 86, Cluster of Differentiation 68, Cluster of Differentiation 163), and proinflammatory cytokines (e.g., interferon gamma, tumor necrosis factor alpha, interferon gamma-induced protein 10).

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

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
Study of PD/PK/PG Relationships of Tacrolimus and Cyclosporin in Liver Transplant Patients	NCT01760356	End Stage Liver... Rejection Infection Malignancy Toxicity Diabetes		18 Years - 70 Years	UDA Centro Nacional Hepato-Bilio-Pancreático
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
CIVO Intratumoural Microdosing of Anti-Cancer Therapies in Australia	NCT04891718	Solid Tumour	MVC-101 Nivolumab MVC-101 + Nivol...	18 Years -	Presage Biosciences
PBI-MST-01(NCT04541108) Substudy TAK-02: Intratumoral Microdosing of TAK-676 in HNSCC	NCT06062602	Head and Neck S...	TAK-676 Carboplatin 5-FU Paclitaxel TAK-676 + Carbo... Carboplatin + P... Carboplatin + 5... TAK-676 + Carbo... TAK-676 + Carbo...	18 Years -	Presage Biosciences

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