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

NCT04541108 | Recruiting Early Phase 1 FDA Drug

• 4 other identifiers: PBI-MST-01MST01-TAK-02 (NCT06062602)MST01-MSD-03MST01-AZN-05 (NCT06366451)
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 12

Brief 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 is a scheduled surgical intervention. CIVO stands for Comparative In Vivo Oncology. Multiple substudies will include specified investigational agents and combinations to be evaluated.

Conditions

Solid Tumor

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

Outcome Measures

Primary Outcomes (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).

  4 hours-7 days after microdose injection

Secondary Outcomes (1)

• Number of Patients with Adverse Events

  Up to 28 days after microdose injection

Study Arms (1)

Rilvegostomig, Volrustomig, Sabestomig, 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, and pembrolizumab alone.

Biological: Rilvegostomig; Biological: Volrustomig; Biological: Sabestomig; Biological: Pembrolizumab

Interventions

Rilvegostomig BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: AZD2936

Rilvegostomig, Volrustomig, Sabestomig, Pembrolizumab

Volrustomig BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: MEDI5752

Rilvegostomig, Volrustomig, Sabestomig, Pembrolizumab

Sabestomig BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: AZD7789

Rilvegostomig, Volrustomig, Sabestomig, Pembrolizumab

Pembrolizumab BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: Keytruda, MK-3475

Rilvegostomig, Volrustomig, Sabestomig, Pembrolizumab

Eligibility Criteria

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

You may not 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 \[solid tumors\] 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:
• 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.
• 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:

Sponsors & Collaborators

• Presage Biosciences: lead

Study Sites (12)

UC Davis

Sacramento, California, 95817, United States

RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, 30308, United States

RECRUITING

LSU Health Sciences Center - Shreveport

Shreveport, Louisiana, 71115, 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

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

WITHDRAWN

UC Health

Cincinnati, Ohio, 45229, United States

COMPLETED

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Sarah Cannon Research Institute

Charleston, South Carolina, 29406, United States

RECRUITING

UT Health

Houston, Texas, 77030, United States

RECRUITING

University of Washington

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (7)

• 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

• 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.

  PMID: 36923556 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Lymphoma; Sarcoma; Melanoma; 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; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

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 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 pembrolizumab. New substudies will be continuously added as they become active.

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: September 9, 2020
• Study Start: July 26, 2021
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: April 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)