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Head and Neck Squamous Cell CarcinomaEarly Phase 1NCT06366451

PBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, Sabestomig, and AZD9592 in HNSCC

A Early Phase 1 study testing Rilvegostomig, Volrustomig and Sabestomig in people with Head and Neck Squamous Cell Carcinoma, run by Presage Biosciences at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multi-center, open-label, Phase 0 substudy designed to evaluate the localized pharmacodynamics (PD) of rilvegostomig, volrustomig, sabestomig, and AZD9592 within the tumor microenvironment (TME) when administered intratumorally in microdose quantities via the CIVO device in patients presenting with Head and… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Squamous Cell Carcinoma
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
17 participants
Where
7 sitesUnited States
Study dates
22 May 2024to 25 Mar 2026
Phase
Early Phase 1
Are there results?
None posted in the registry

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 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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  • Male or female ≥ 18 years of age at Visit 1 (Screening).
  • Pathologic diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC) of the oropharynx, hypopharynx, oral cavity, or larynx.
  • Ability and willingness to comply with the study's visits and assessment schedule.
  • At least one lesion (primary tumor, recurrent tumor, metastasis, 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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  • Female patients who:
  • 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) until 7 months after the CIVO injection OR agree to completely abstain from heterosexual intercourse.
  • Agree to refrain from donating, or retrieving for their own use, ova until 7 months after the CIVO injection.
  • Agree to refrain from breastfeeding until 7 months after the CIVO injection.
  • 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 until 7 months after the CIVO injection OR agree to completely abstain from heterosexual intercourse.
  • Agree to refrain from fathering a child or donating sperm until 7 months after the CIVO injection.

Who cannot join

  • Tumors and/or effaced nodes that are anticipated by the Investigator to lack a sufficient volume of viable tumor tissue (Based on available pre-operative imaging, pre-injection ultrasound imaging, or pathology reports) for CIVO microdose injection due to necrosis, cysts, excessive stroma, fibrosis, or treatment-induced tissue changes.
  • Tumors near or involving critical structures for which, in the opinion of the treating clinician, injection would pose undue risk to the patient.
  • Prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies within the last 5 years.
  • Previous treatment with another ADC containing a chemotherapeutic agent that inhibits topoisomerase 1 activity or with another epidermal growth factor receptor (EGFR) and/or mesenchymal-epithelial transition factor (c-MET) targeted ADC.
  • Patients with concurrent cancer, immune disease or active infection requiring systemic or radiotherapy.
  • Female patients who:
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  • Intend to become pregnant during the study,
  • Are both lactating and breastfeeding, OR
  • Have a positive beta-subunit human chorionic gonadotropin (beta-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.
  • History of organ transplant.
  • Major surgery within 4 weeks prior to injection: subject must have adequate wound healing and have recovered from any prior surgery.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Sarah Cannon Medical Center

    Charleston, South Carolina, 29406

  • Medical University of South Carolina

    Charleston, South Carolina, 29407

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19107

  • Oregon Health & Science University (OHSU)

    Portland, Oregon, 97239

  • UC Davis

    Sacramento, California, 95817

  • Montefiore Medical Center

    The Bronx, New York, 10467

Other trials in United States

About this study

Official title: A Phase 0 Multicenter Study of the Pharmacodynamic Effects of Intratumoral Microdose Administration of Rilvegostomig, Volrustomig, Sabestomig, and AZD9592

This is a multi-center, open-label, Phase 0 substudy designed to evaluate the localized pharmacodynamics (PD) of rilvegostomig, volrustomig, sabestomig, and AZD9592 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, either as single agents or as AZD9592 drug combinations with the evaluated biologics, will be compared to those elicited by pembrolizumab alone, which will also be injected in microdose quantities via the CIVO device.

Read the detailed description

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. In addition, microdoses of AZD9592, a novel antibody drug conjugate (ADC), alone or in combinations with the evaluated biologics will also be assessed. The CIVO-injected portion of the tissue will be analyzed for localized response at sites of drug exposure in the TME.

Being tested
Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab
Keywords
HNSCC, intratumoral microdosing, microdose injection, microdosing, in vivo oncology, tumor microenvironment, multiplexed immunohistochemistry, head and neck cancer, head and neck squamous cell carcinoma, pharmacodynamic biomarkers, CIVO, master protocol, precision oncology, spatial biology
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, 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.

  • AZD9592Biological

    Intratumoral microdose injection by the CIVO device.

  • PembrolizumabBiological

    Also called Keytruda, MK-3475

    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 NCT06366451
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: AZD9592; Biological: Pembrolizumab; 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. Evaluation of signature scores using Gene Set Variability Analysis within regions injected with microdoses of rilvegostomig, volrustomig, sabestomig, AZD9592, or pembrolizumab as single agents or as AZD9592 drug combinations with the evaluated biologics

    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, immunofluorescence, or ISH technique.

    Measured: 1 to 3 days after microdose injection

Secondary outcomes (1)

  1. Incidence of reported Adverse Events and/or Adverse Device Effects [Safety and Tolerability]

    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.

    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 posted16 Apr 2024
  2. Study start22 May 2024
  3. Primary completion25 Mar 2026
  4. Study completion25 Mar 2026

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 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.
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06366451
Sponsor's protocol ID
MST01-AZN-05
Other IDs
PBI-MST-01
Status last verified
Jun 2026
First submitted
3 Apr 2024
Last updated
26 Jun 2026
Results posted
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

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Rilvegostomig, Volrustomig and Sabestomig in people with Head and Neck Squamous Cell Carcinoma, run by Presage Biosciences at 7 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 15 inclusion and 12 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: finished, as of the sponsor's last update on 26 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Evaluation of signature scores using Gene Set Variability Analysis within regions injected with microdoses of rilvegostomig, volrustomig, sabestomig, AZD9592, or pembrolizumab as single agents or as AZD9592 drug combinations with the evaluated biologics (time frame: 1 to 3 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 NCT06366451, which also lists 6 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 26 Jun 2026.

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