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

NCT06413095 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: MST01-MSD-03PBI-MST-01
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 11

Brief 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 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.

Conditions

Head and Neck Squamous Cell Carcinoma; Soft Tissue Sarcoma

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

Outcome Measures

Primary Outcomes (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).

  2 to 4 days after microdose injection

Secondary Outcomes (1)

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

  Up to 28 days after microdose injection

Study Arms (1)

Pembrolizumab Alone or in Combination with MK-0482 or MK-4830

EXPERIMENTAL

Patient 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.

Biological: Pembrolizumab; Combination Product: MK-0482 + Pembrolizumab; Combination Product: MK-4830 + Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: Keytruda, MK-3475

Pembrolizumab Alone or in Combination with MK-0482 or MK-4830

MK-0482 + Pembrolizumab COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

Pembrolizumab Alone or in Combination with MK-0482 or MK-4830

MK-4830 + Pembrolizumab COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

Pembrolizumab Alone or in Combination with MK-0482 or MK-4830

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Presage Biosciences: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (11)

UC Davis

Sacramento, California, 95817, United States

Location

Emory Winship Cancer Institute

Atlanta, Georgia, 30308, United States

Location

LSU Health Sciences Center - Shreveport

Shreveport, Louisiana, 71115, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

UC Health

Cincinnati, Ohio, 45219, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Sarah Cannon Medical Center

Charleston, South Carolina, 29406, United States

Location

UT Health Houston

Houston, Texas, 77401, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Related Publications (6)

• 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.

  PMID: 37389981 BACKGROUND

• 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.

  PMID: 32299817 BACKGROUND

• 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.

  PMID: 25904742 BACKGROUND

• 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.

  PMID: 28364003 BACKGROUND

• 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.

  PMID: 27359113 BACKGROUND

• 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.

  PMID: 27308571 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Sarcoma; Head and Neck Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Connective and Soft Tissue

Study Officials

• Study Director

  Presage Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 1, 2024
• First Posted: May 14, 2024
• Study Start: June 1, 2022
• Primary Completion: June 22, 2023
• Study Completion: June 22, 2023
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)