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Solid TumorEarly Phase 1NCT04541108

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

A Early Phase 1 study testing Rilvegostomig, Volrustomig and Sabestomig in people with Solid Tumor, run by Presage Biosciences at 9 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
Rilvegostomig, Volrustomig and Sabestomig
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
9 sitesUnited States
Study dates
26 Jul 2021to Dec 2031
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ability and willingness to comply with the study's visit and assessment schedule.
  • Male or female ≥ 18 years of age at Visit 1 (Screening).
  • Pathologic diagnosis of [solid tumors] indicated in the relevant substudy(ies).
  • Ability and willingness to provide written informed consent. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  • At least one lesion (primary tumor, recurrent tumor, or metastatic lymph node) that is surface accessible for CIVO injection that contains viable minimum tumor tissue volume and characteristics (e.g., based on clinical evaluation, available pre-operative imaging, pre-injection ultrasound imaging, or pathology reports indicating lesion with appropriate viable tumor volume without excessive cysts or necrosis) and for which there is a planned surgical intervention. The patient's presentation, surgical and pathology plan may determine whether a lesion is eligible with respect to a given CIVO MID needle configuration.
  • Female patients who:
Show all 13Show fewer
  • Are postmenopausal for at least one year before the screening visit, OR
  • Are surgically sterile, OR
  • Are of childbearing potential who agree to practice a highly effective method of contraception from the time of signing the Informed Consent Form (ICF) and during study participation OR agree to completely abstain from heterosexual intercourse.
  • Agree to refrain from donating ova during study participation.
  • Male patients, even if surgically sterile (i.e., status post-vasectomy), who:
  • Agree to practice effective barrier contraception from the time of signing the ICF and during study participation OR agree to completely abstain from heterosexual intercourse.
  • Agree to refrain from donating sperm during study participation.

Who cannot join

  • Tumors near or involving critical structures for which, in the opinion of the treating clinician, injection would pose undue risk to the patient.
  • Female patients who are:
  • Both lactating and breastfeeding, OR
  • Have a positive β-subunit human chorionic gonadotropin (β-hCG) pregnancy test at screening verified by the Investigator.
  • 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Sarah Cannon Research Institute

    Charleston, South Carolina, 29406

  • MUSC Hollings Cancer Center

    Charleston, South Carolina, 29425

  • UC Health

    Cincinnati, Ohio, 45229

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19107

  • Oregon Health & Science University (OHSU)

    Portland, Oregon, 97239

  • University of Washington

    Seattle, Washington, 98109

  • LSU Health Sciences Center - Shreveport

    Shreveport, Louisiana, 71115

  • Montefiore Medical Center

    The Bronx, New York, 10467

Other trials in United States

About this study

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

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.

Read the detailed description

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.

Conditions
Solid Tumor
Being tested
Rilvegostomig, Volrustomig, Sabestomig, Pembrolizumab, AZD9592
Keywords
HNSCC, SCCHN, lymphoma, sarcoma, breast adenocarcinoma, melanoma, intratumoral microdosing, microdose injection, microdosing, in vivo oncology, in vivo drug sensitivity, tumor microenvironment, multiplexed immunohistochemistry, head and neck cancer, pharmacodynamic biomarkers, CIVO, master protocol, precision oncology, soft tissue sarcoma, spatial biology
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Lymphoma, Sarcoma, Melanoma, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RilvegostomigBiological

    Also called AZD2936

    Intratumoral microdose injection by the CIVO device.

  • VolrustomigBiological

    Also called MEDI5752

    Intratumoral microdose injection by the CIVO device.

  • SabestomigBiological

    Also called AZD7789

    Intratumoral microdose injection by the CIVO device.

  • PembrolizumabBiological

    Also called Keytruda, MK-3475

    Intratumoral microdose injection by the CIVO device.

  • AZD9592Biological

    Intratumoral microdose injection by the CIVO device

  • AZD9592 + RilvegostomigCombination product

    Intratumoral microdose injection by the CIVO device

  • AZD9592 + VolrustomigCombination product

    Intratumoral microdose injection by the CIVO device

  • AZD9592 + SabestomigCombination product

    Intratumoral microdose injection by the CIVO device

  • AZD9592 + PembrolizumabCombination product

    Intratumoral microdose injection by the CIVO device

Study groups in NCT04541108
Study groupRoleWhat they receive
Rilvegostomig, Volrustomig, Sabestomig, AZD9592, PembrolizumabExperimentalHNSCC 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, AZD9592, and pembrolizumab as single agents and AZD9592 drug combinations with the evaluated biologics.
Receives: Biological: Rilvegostomig; Biological: Volrustomig; Biological: Sabestomig; Biological: Pembrolizumab; Biological: AZD9592; Combination Product: AZD9592 + Rilvegostomig; Combination Product: AZD9592 + Volrustomig; Combination Product: AZD9592 + Sabestomig; Combination Product: AZD9592 + Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Quantification of Selected Pharmacodynamic Biomarkers as Specified in Substudies by IHC, ISH, and/or Spatial Biology Platforms

    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).

    Measured: 4 hours-7 days after microdose injection

Secondary outcomes (1)

  1. Number of Patients with Adverse Events

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

    Measured: Up to 28 days after microdose injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2020
  2. Study start26 Jul 2021
  3. Primary completionDec 2031 (estimated)
  4. Study completionDec 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Model description
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 AZD9592 in HNSCC. New substudies will be continuously added as they become active.
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04541108
Sponsor's protocol ID
PBI-MST-01
Other IDs
MST01-TAK-02 (NCT06062602), MST01-MSD-03 (NCT04541108), MST01-AZN-05 (NCT06366451)
Status last verified
May 2026
First submitted
1 Sep 2020
Last updated
22 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Derry JMJ, Burns C, Frazier JP, Beirne E, Grenley M, DuFort CC, Killingbeck E, Leon M, Williams C, Gregory M, Houlton J, Clayburgh D, Swiecicki P, Huszar D, Berger A, Klinghoffer RA. Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment. Clin Cancer Res. 2023 Sep 15;29(18):3813-3825. doi: 10.1158/1078-0432.CCR-23-0827.

    PubMed 37389981

  • Gundle KR, Deutsch GB, Goodman HJ, Pollack SM, Thompson MJ, Davis JL, Lee MY, Ramirez DC, Kerwin W, Bertout JA, Grenley MO, Sottero KHW, Beirne E, Frazier J, Dey J, Ellison M, Klinghoffer RA, Maki RG. Multiplexed Evaluation of Microdosed Antineoplastic Agents In Situ in the Tumor Microenvironment of Patients with Soft Tissue Sarcoma. Clin Cancer Res. 2020 Aug 1;26(15):3958-3968. doi: 10.1158/1078-0432.CCR-20-0614. Epub 2020 Apr 16.

    PubMed 32299817

  • Klinghoffer RA, Bahrami SB, Hatton BA, Frazier JP, Moreno-Gonzalez A, Strand AD, Kerwin WS, Casalini JR, Thirstrup DJ, You S, Morris SM, Watts KL, Veiseh M, Grenley MO, Tretyak I, Dey J, Carleton M, Beirne E, Pedro KD, Ditzler SH, Girard EJ, Deckwerth TL, Bertout JA, Meleo KA, Filvaroff EH, Chopra R, Press OW, Olson JM. A technology platform to assess multiple cancer agents simultaneously within a patient's tumor. Sci Transl Med. 2015 Apr 22;7(284):284ra58. doi: 10.1126/scitranslmed.aaa7489.

    PubMed 25904742

  • Frazier JP, Bertout JA, Kerwin WS, Moreno-Gonzalez A, Casalini JR, Grenley MO, Beirne E, Watts KL, Keener A, Thirstrup DJ, Tretyak I, Ditzler SH, Tripp CD, Choy K, Gillings S, Breit MN, Meleo KA, Rizzo V, Herrera CL, Perry JA, Amaravadi RK, Olson JM, Klinghoffer RA. Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation. Cancer Res. 2017 Jun 1;77(11):2869-2880. doi: 10.1158/0008-5472.CAN-17-0084. Epub 2017 Mar 31.

    PubMed 28364003

  • Dey J, Kerwin WS, Grenley MO, Casalini JR, Tretyak I, Ditzler SH, Thirstrup DJ, Frazier JP, Pierce DW, Carleton M, Klinghoffer RA. A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo. PLoS One. 2016 Jun 30;11(6):e0158617. doi: 10.1371/journal.pone.0158617. eCollection 2016.

    PubMed 27359113

  • Moreno-Gonzalez A, Olson JM, Klinghoffer RA. Predicting responses to chemotherapy in the context that matters - the patient. Mol Cell Oncol. 2015 Jun 10;3(1):e1057315. doi: 10.1080/23723556.2015.1057315. eCollection 2016 Jan.

    PubMed 27308571

  • Carideo Cunniff E, Sato Y, Mai D, Appleman VA, Iwasaki S, Kolev V, Matsuda A, Shi J, Mochizuki M, Yoshikawa M, Huang J, Shen L, Haridas S, Shinde V, Gemski C, Roberts ER, Ghasemi O, Bazzazi H, Menon S, Traore T, Shi P, Thelen TD, Conlon J, Abu-Yousif AO, Arendt C, Shaw MH, Okaniwa M. TAK-676: A Novel Stimulator of Interferon Genes (STING) Agonist Promoting Durable IFN-dependent Antitumor Immunity in Preclinical Studies. Cancer Res Commun. 2022 Jun 23;2(6):489-502. doi: 10.1158/2767-9764.CRC-21-0161. eCollection 2022 Jun.

    PubMed 36923556

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Rilvegostomig, Volrustomig and Sabestomig in people with Solid Tumor, run by Presage Biosciences at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Quantification of Selected Pharmacodynamic Biomarkers as Specified in Substudies by IHC, ISH, and/or Spatial Biology Platforms (time frame: 4 hours-7 days after microdose injection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04541108, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.

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