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

NCT06366451 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: MST01-AZN-05PBI-MST-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 7

Brief 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 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.

Conditions

Head and Neck Squamous Cell Carcinoma

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

Outcome Measures

Primary Outcomes (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.

  1 to 3 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

Other Outcomes (1)

• Evaluation of tumor whole exome sequencing (WES)/whole transcriptome sequencing (WTS)

  Sample collected at screening

Study Arms (1)

Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab

EXPERIMENTAL

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, AZD9592, and pembrolizumab as single agents and AZD9592 drug combinations with the evaluated biologics.

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

Interventions

Rilvegostomig BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: AZD2936

Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab

Volrustomig BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: MEDI5752

Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab

Sabestomig BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: AZD7789

Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab

AZD9592 BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab

Pembrolizumab BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: Keytruda, MK-3475

Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab

AZD9592 + Rilvegostomig COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab

AZD9592 + Volrustomig COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab

AZD9592 + Sabestomig COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab

AZD9592 + Pembrolizumab COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab

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 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.
• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Presage Biosciences: lead
• AstraZeneca: collaborator

Study Sites (7)

UC Davis

Sacramento, California, 95817, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

NOT YET RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Sarah Cannon Medical Center

Charleston, South Carolina, 29406, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29407, United States

RECRUITING

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; 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

Study Officials

• Study Director

  Presage Biosciences

  STUDY DIRECTOR

Central Study Contacts

Presage Biosciences

CONTACT

800-530-5404; clinops@presagebio.com

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 3, 2024
• First Posted: April 16, 2024
• Study Start: May 22, 2024
• Primary Completion: February 1, 2025
• Study Completion: April 1, 2025
• Last Updated: January 20, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)