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Head and Neck Squamous Cell CarcinomaEarly Phase 1NCT06413095

PBI-MST-01 (NCT04541108) Substudy MSD-03: Intratumoral Microdosing of Pembrolizumab Alone and With MK-0482 or MK-4830 in HNSCC or STS

A Early Phase 1 study testing Pembrolizumab, MK-0482 + Pembrolizumab and MK-4830 + Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma and Soft Tissue Sarcoma, run by Presage Biosciences at 11 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 ability of pembrolizumab, alone and in combination with MK-0482 or MK-4830, to elicit pharmacodynamic changes suggestive of antitumor immune activation within the native tumor microenvironment (TME) following intratumoral microdosing via the… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab, MK-0482 + Pembrolizumab and MK-4830 + Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
11 sitesUnited States
Study dates
1 Jun 2022to 22 Jun 2023
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 comply with the study's visit and assessment schedule.
  • Male or female ≥18 years of age at Visit 1 (Screening).
  • Pathologic diagnosis of HNSCC or STS.
  • 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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.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) of at least approximately 2.5 cm in the shortest diameter that is surface accessible for CIVO injection that contains viable minimum tissue volume and characteristics (e.g., based on clinical evaluation, available pre-operative imaging, pre-injection ultrasound imaging, or pathology reports indication lesion with appropriate viable tumor volume, without excessive cysts or necrosis) and for which there is a planned surgical intervention.
  • Female patients who:
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  • 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) through up to 120 days after the tumor injection procedure 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Who cannot join

  • Patients who have received neoadjuvant therapy associated with the surgical intervention described in Inclusion Criterion #5 within 6 months of the CIVO injection procedure.
  • 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 beta 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.
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  • Patients with a history of concurrent second cancers requiring active, ongoing systemic treatment. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Patients with a diagnosis of immunodeficiency.
  • Patients with known HIV/AIDS with uncontrolled viral load and CD4 less than 200, or those with concurrent active hepatitis B (defined as HBsAg positive or detectable HBV DNA) or hepatitis C (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: HIV infected participants with a history of Kaposi's sarcoma or Multicentric Castleman's Disease are excluded. Hepatitis B and C screening tests are not required unless:
  • Patient has a known history of hepatitis B/C infection
  • Mandated by local health authority
  • Patients that have received a live or live-attenuated vaccine within 4 weeks of the baseline/screening visit.
  • Use of any of the following ≤ 2 weeks prior to CIVO injection:
  • Chronic systemic immunosuppressive therapy or corticosteroids (in dosing exceeding 10 mg daily of prednisone equivalent). Intranasal, inhaled, topical, or local corticosteroid injections (e.g., intra-articular injection), or steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication) are exceptions to this criterion.
  • Biological response modifiers for treatment of active autoimmune disease.
  • Hematopoietic growth factors.
  • Patients who have received prior treatment with radiation or systemic therapy (e.g., cytotoxic chemotherapy, targeted agents, or checkpoint inhibitor immunotherapy, etc.), or have participated in a study of an investigational device within 6 months of the CIVO injection procedure. Note: Participants must have recovered from all radiation-related toxicities, must not require corticosteroids, and must not have had radiation pneumonitis.
  • Patients who have a history of (noninfectious) pneumonitis that required steroids or have current pneumonitis.
  • Patients who have had allogenic tissue/solid organ transplant.
  • Patients who have had severe hypersensitivity (≥Grade 3) to pembrolizumab, MK-4830, MK-0482, or any of their excipients.
  • Patients with an active infection requiring systemic therapy.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Emory Winship Cancer Institute

    Atlanta, Georgia, 30308

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Sarah Cannon Medical Center

    Charleston, South Carolina, 29406

  • UC Health

    Cincinnati, Ohio, 45219

  • UT Health Houston

    Houston, Texas, 77401

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19107

  • Oregon Health & Science University (OHSU)

    Portland, Oregon, 97239

  • UC Davis

    Sacramento, California, 95817

  • 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: Pembrolizumab Alone and in Combination(s) With MK-0482 and MK-4830 Via Intratumoral Injection in Patients With Head and Neck Squamous Cell Carcinoma or Soft Tissue Sarcoma Prior to Planned Surgical Intervention

This is a multi-center, open-label, Phase 0 substudy designed to evaluate the ability of pembrolizumab, alone and in combination with MK-0482 or MK-4830, to elicit pharmacodynamic changes suggestive of antitumor immune activation within the native tumor microenvironment (TME) following intratumoral microdosing via the CIVO device in patients with surface accessible Head and Neck Squamous Cell Carcinoma (HNSCC) or Soft Tissue Sarcoma (STS) lesion(s) who are scheduled for tumor and/or regional node dissection as part of their standard treatment.

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. The microdose injection procedure is conducted ahead of the patient's scheduled surgical intervention and localized biomarker responses are then evaluated in the injected tumor tissue following surgery. This enables assessments of drug-induced changes to the tumor, stroma, and local immune cells within the unique landscape of each individual patient and their respective tumor genomic profile and immune system functional status. CIVO is a research tool used only to assess the responses of tumor cells and other cell populations with the TME following intratumoral administration of drug microdoses; it is not a therapeutic device.

MK-0482, MK-4830, and pembrolizumab have distinct mechanisms of action (MOAs) that affect the TME, including relief of immune suppression and enhanced T-cell activation. Surgery is the standard primary treatment for most patients with STS, and surgical intervention of the primary tumor and cervical lymph node dissection may be recommended for patients with HNSCC. Dysfunction of the immune system (e.g., immune evasion, expression of suppressive immune checkpoint receptors, etc.) plays a major role in the development and progression of HNSCC and STS. Therefore, in this Phase 0 study, the ability of pembrolizumab, alone and in combination with MK-0482 or MK-4830, to elicit pharmacodynamic changes suggestive of antitumor immune activation within the native TME in patients with HNSCC or STS will be assessed. Pembrolizumab, alone and in combination with MK-0482 or MK-4830, will be injected in microdose quantities at tumor sites in HNSCC or STS patients with a surface accessible lesion who are scheduled for tumor and/or regional node dissection as part of their standard treatment. Injected tumors will be resected as per surgical standard of care following 2 to 4 days in situ exposure. Thereafter, the CIVO-injected portion of the tissue will be analyzed for localized response at sites of drug exposure in the TME.

Being tested
Pembrolizumab, MK-0482 + Pembrolizumab, MK-4830 + Pembrolizumab
Keywords
HNSCC, head and neck cancer, head and neck squamous cell carcinoma, STS, soft tissue sarcoma, intratumoral microdosing, microdose injection, microdosing, in vivo oncology, tumor microenvironment, multiplexed immunohistochemistry, pharmacodynamic biomarkers, CIVO, master protocol, precision oncology, spatial biology
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Sarcoma, Head and Neck Neoplasms

What participants receive

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

  • PembrolizumabBiological

    Also called Keytruda, MK-3475

    Intratumoral microdose injection by the CIVO device.

  • MK-0482 + PembrolizumabCombination product

    Intratumoral microdose injection by the CIVO device.

  • MK-4830 + PembrolizumabCombination product

    Intratumoral microdose injection by the CIVO device.

Study groups in NCT06413095
Study groupRoleWhat they receive
Pembrolizumab Alone or in Combination with MK-0482 or MK-4830ExperimentalPatient with HNSCC or STS with surface accessible lesions who are scheduled for tumor or regional node dissection as part of their standard treatment will be injected two 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 pembrolizumab as a single agent or in combination with MK-0482 or MK-4830. Each microdose is simultaneously injected in a columnar fashion through each of 5 or 8 needles by the CIVO Micodose Injection Device (MID) into a single solid tumor or effaced metastatic lymph node.
Receives: Biological: Pembrolizumab; Combination Product: MK-0482 + Pembrolizumab; Combination Product: MK-4830 + Pembrolizumab

What is being measured

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

  1. Quantification of Immune Cell Biomarkers by Immunohistochemistry (IHC), In Situ Hybridization (ISH), and/or Spatial Biology Platforms

    Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumor microenvironment around injection sites in resected patient samples 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, markers associated with macrophage polarization states (e.g., CD163), markers of infiltrating T cells (e.g., CD8/Granzyme B), and proinflammatory cytokines (e.g., interferon gamma).

    Measured: 2 to 4 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 posted14 May 2024
  2. Study start1 Jun 2022
  3. Primary completion22 Jun 2023
  4. Study completion22 Jun 2023

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
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06413095
Sponsor's protocol ID
MST01-MSD-03
Other IDs
PBI-MST-01
Status last verified
May 2024
First submitted
1 Apr 2024
Last updated
14 May 2024
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 Pembrolizumab, MK-0482 + Pembrolizumab and MK-4830 + Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma and Soft Tissue Sarcoma, run by Presage Biosciences at 11 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 14 inclusion and 21 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 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 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?

Quantification of Immune Cell Biomarkers by Immunohistochemistry (IHC), In Situ Hybridization (ISH), and/or Spatial Biology Platforms (time frame: 2 to 4 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 NCT06413095, 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 14 May 2024.

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