Intratumoral Microdosing for Cancer

Recruiting at 11 trial locations

Overseen By Roxanne Moore

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Presage Biosciences

Disqualifiers: Pregnancy, Breastfeeding, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 week

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of small doses of cancer drugs injected directly into tumors using the CIVO Intratumoral Microdosing platform. Researchers aim to observe how these drugs impact the tumor environment and may explore different drug combinations. Individuals with accessible solid tumors scheduled for surgery might be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants an opportunity to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that the CIVO device is safe for intratumoral microdosing?

Research has shown that the CIVO method, which delivers tiny doses of cancer drugs directly into tumors, is generally safe. The CIVO device underwent testing in six clinical trials with 68 patients, using both new and existing cancer drugs. Results indicate that it is safe and practical for this purpose. Specifically, in studies with patients who have soft tissue sarcoma, the CIVO device did not cause serious side effects.

For those considering joining a trial, these findings suggest that the CIVO method is well-tolerated. However, discussing any concerns with a medical team is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CIVO Intratumoral Microdosing for treating head and neck squamous cell carcinoma (HNSCC) because it allows for direct delivery of multiple cancer drugs, like rilvegostomig, volrustomig, sabestomig, and pembrolizumab, straight into the tumor. This method potentially maximizes effectiveness while minimizing side effects, a significant improvement over traditional systemic therapies like chemotherapy and radiation. Additionally, CIVO's ability to test multiple drugs simultaneously helps identify the most effective treatment in a much shorter time frame, offering personalized therapy options faster than ever before.

What evidence suggests that this trial's treatments could be effective for cancer?

Research shows that CIVO intratumoral microdosing allows doctors to test how different cancer drugs affect a tumor by injecting tiny doses directly into it. In this trial, participants will receive microdoses of rilvegostomig, volrustomig, sabestomig, and pembrolizumab using the CIVO device. Studies have found that CIVO can safely deliver up to eight different drugs or combinations simultaneously. This method helps doctors identify which drugs might work best without affecting the rest of the body. Previous trials with the CIVO device safely involved 68 patients using various cancer drugs. Although still in early stages, this approach appears promising for targeting cancer more precisely and with fewer side effects. ^{2 3 4 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Presage Biosciences

Are You a Good Fit for This Trial?

Adults with surface accessible solid tumors scheduled for surgery can join. They must be able to follow the study plan and agree to use effective contraception or abstain from sex. Excluded are those with tumors near critical structures, pregnant or breastfeeding women, and anyone with serious illnesses that could affect participation.

Inclusion Criteria

Ability and willingness to comply with the study's visit and assessment schedule

My cancer type matches one of the study's specific cancer types.

I am willing and able to sign a consent form for the study.

Exclusion Criteria

My doctor thinks it's too risky to inject my tumor due to its location.

Any uncontrolled intercurrent illness, condition, serious medical or psychiatric illness, or circumstance that, in the opinion of the Investigator, could interfere with adherence to the study's procedures or requirements, or otherwise compromise the study's objectives.

I am currently breastfeeding or have tested positive for pregnancy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intratumoral microdoses of anti-cancer therapies using the CIVO device

1 week

1 visit (in-person)

Surgical Intervention

Surgical excision of the tumor is performed to assess tumor responses to the microdoses

4 hours to 7 days after microdose injection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 5-FU
• Carboplatin
• CIVO Intratumoral Microdosing
• Ipilimumab
• Nivolumab
• Paclitaxel
• Pembrolizumab

Trial Overview The trial tests how anti-cancer drugs like Pembrolizumab and its combinations work inside tumors when given in tiny amounts using a device called CIVO before surgical removal of the tumor. It aims to understand drug effects directly within the tumor environment.

How Is the Trial Designed?

Group I: Rilvegostomig, Volrustomig, Sabestomig, Pembrolizumab Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

Presage Biosciences

Lead Sponsor

Trials

10

Recruited

110+

Takeda

Industry Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase 0 clinical trial involving 12 patients with head and neck carcinoma, the investigational drug subasumstat was shown to effectively inhibit the SUMO pathway and induce an immune response within localized tumor regions, demonstrating its potential efficacy in treating cancer.

The innovative combination of trackable intratumor microdosing and spatial biology allowed researchers to assess the drug's effects directly in patient tumors, revealing specific mechanisms of action such as cell cycle inhibition and a shift in the tumor microenvironment from immune-suppressive to immune-permissive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment. Derry, JMJ., Burns, C., Frazier, JP., et al.[2023]

The CIVO technology platform allows for the simultaneous assessment of multiple cancer drugs directly within a single tumor, providing a more accurate representation of drug efficacy compared to traditional in vitro models.

In studies using CIVO, localized drug responses were observed that predicted systemic drug effectiveness, revealing important insights into tumor resistance and sensitivity, which could lead to more effective personalized cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A technology platform to assess multiple cancer agents simultaneously within a patient's tumor. Klinghoffer, RA., Bahrami, SB., Hatton, BA., et al.[2022]

Microdosing allows researchers to test potential drug compounds in humans before Phase I trials, helping to identify ineffective drugs early in the development process and streamline the drug pipeline.

This method provides valuable data on how drugs are absorbed and distributed in the body, potentially reducing development timelines and costs, although more research is needed to fully understand its impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdosing in early lead discovery. Jekunen, AP., Pauwels, EK., Kairemo, KJ.[2010]

Microdosing, which involves administering a very small dose of a drug (1% of the pharmacologic dose or 100 µg), has shown that about 80% of orally tested drugs and 100% of intravenously tested drugs maintain predictable pharmacokinetics (PK) between microdoses and therapeutic doses, which is crucial for drug development.

Recent advancements in microdosing techniques have expanded its applications, including in pediatrics and localized treatments, suggesting it may offer a more effective way to understand drug behavior in humans before moving to larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The expanding utility of microdosing. Lappin, G.[2018]

CIVO technology allows for the simultaneous analysis of up to 8 different therapies directly within a patient's tumor, providing a more accurate understanding of how tumors respond to treatments.

This method avoids systemic toxicity and preserves the natural tumor microenvironment, making it a safer and more effective way to study cancer therapies in real patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting responses to chemotherapy in the context that matters - the patient. Moreno-Gonzalez, A., Olson, JM., Klinghoffer, RA.[2020]

The Comparative In Vivo Oncology (CIVO) system was found to be safe and feasible in a pilot study involving 13 patients with soft tissue sarcoma, with only minor, transient adverse events reported.

CIVO allowed for the simultaneous testing of multiple microdoses of anticancer drugs directly in the tumor, showing consistent drug responses that align with known mechanisms of action, which could enhance early evaluation of new cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiplexed Evaluation of Microdosed Antineoplastic Agents In Situ in the Tumor Microenvironment of Patients with Soft Tissue Sarcoma. Gundle, KR., Deutsch, GB., Goodman, HJ., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04272333

Intratumoral Microdosing of Motolimod in HNSCC The CIVO device penetrates solid tumors and delivers subtherapeutic microdoses of up to eight anti-cancer agents or combinations of anti-cancer agents co- ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.e23569

Multidrug analyses in cancer patients via intratumoral ... We developed CIVO (Comparative In Vivo Oncology), an arrayed microinjection technology that evaluates tumor responsiveness to microdoses of multiple drugs ...

3. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/620/703823/Abstract-620-Intratumoral-microdosing-via-the

Abstract 620: Intratumoral microdosing via the CIVO® Platform ... The CIVO (Comparative In Vivo Oncology) platform can simultaneously deliver up to 8 drugs and combinations in microdose amounts to distinct ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04065555

Intratumoral Microdosing of TAK-981 in Head and Neck ... This is a multi-center, single arm, open-label, multi-agent, localized pharmacodynamic biomarker Phase 0 trial designed to study the biological effects ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11048044/

Early, precise, and safe clinical evaluation of the ... Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04541108

Phase 0 Master Protocol for CIVO Intratumoral Microdosing ... The CIVO device penetrates solid tumors and simultaneously delivers subtherapeutic microdoses of up to eight anti-cancer agents or combinations of anti-cancer ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301621033563

A Phase 0 Master Protocol Utilizing a Novel Intratumoral ... CIVO (Comparative In Vivo Oncology) is an intratumoral microdose injection research tool intended to bridge the translational gap between preclinical and ...