PBI-MST-01(NCT04541108) Substudy TAK-02: Intratumoral Microdosing of TAK-676 in HNSCC

NCT06062602 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: MST01-TAK-02PBI-MST-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multi-center, open-label Phase 0 substudy designed to study the localized pharmacodynamics (PD) of TAK-676 alone or in combination with Carboplatin, 5-FU, or Paclitaxel within the tumor microenvironment (TME) when administered intratumorally in microdose quantities via the CIVO device in patients diagnosed with Head and Neck Squamous Cell Carcinoma presenting with a surface accessible solid tumor for which there is a scheduled surgical intervention. This substudy is a cohort of the PBI-MST-01 Master Protocol.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

HNSCC; 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; spatial biology

Outcome Measures

Primary Outcomes (1)

• Quantification of Cell Death and Immune Cell Biomarkers by immuno-histochemistry (IHC) and In-Situ Hybridization (ISH)

  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 and ISH. 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., Cluster of Differentiation 3 (CD3), Cluster of Differentiation 8/Granzyme B, Cluster of Differentiation), natural killer (NK)/myeloid cells (e.g., Cluster of Differentiation 56/Granzyme B, Cluster of Differentiation 86, Cluster of Differentiation 68, Cluster of Differentiation 163), and proinflammatory cytokines (e.g., interferon gamma, tumor necrosis factor alpha, interferon gamma-induced protein 10).

  4 hours - 4 days after microdose injection

Secondary Outcomes (1)

• Number of Patients with Adverse Events

  Up to 28 days after microdose injection

Study Arms (1)

TAK-676, Carboplatin, 5-FU, & Paclitaxel

EXPERIMENTAL

Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected at least four hours to up 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 TAK-676, carboplatin, 5-fluorouracil (5- FU), or paclitaxel as single agents or in combination. Each microdose is simultaneously injected in a columnar fashion through each of 8, 5, or 3 needles (in a device configuration determined by tumor dimensions) into a single solid tumor or effaced metastatic lymph node.

Drug: TAK-676; Drug: Carboplatin; Drug: 5-FU; Drug: Paclitaxel; Combination Product: TAK-676 + Carboplatin; Combination Product: Carboplatin + Paclitaxel; Combination Product: Carboplatin + 5-FU; Combination Product: TAK-676 + Carboplatin + 5-FU; Combination Product: TAK-676 + Carboplatin + Paclitaxel

Interventions

TAK-676 DRUG

Intratumoral microdose injection by the CIVO device.

TAK-676, Carboplatin, 5-FU, & Paclitaxel

Carboplatin DRUG

Intratumoral microdose injection by the CIVO device.

Also known as: Paraplatin

TAK-676, Carboplatin, 5-FU, & Paclitaxel

5-FU DRUG

Intratumoral microdose injection by the CIVO device.

Also known as: Adrucil

TAK-676, Carboplatin, 5-FU, & Paclitaxel

Paclitaxel DRUG

Intratumoral microdose injection by the CIVO device.

Also known as: Taxol

TAK-676, Carboplatin, 5-FU, & Paclitaxel

TAK-676 + Carboplatin COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

TAK-676, Carboplatin, 5-FU, & Paclitaxel

Carboplatin + Paclitaxel COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

TAK-676, Carboplatin, 5-FU, & Paclitaxel

Carboplatin + 5-FU COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

TAK-676, Carboplatin, 5-FU, & Paclitaxel

TAK-676 + Carboplatin + 5-FU COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

TAK-676, Carboplatin, 5-FU, & Paclitaxel

TAK-676 + Carboplatin + Paclitaxel COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

TAK-676, Carboplatin, 5-FU, & Paclitaxel

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 Head and Neck Squamous Cell Carcinoma (HNSCC).
• 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 effaced metastatic lymph node) ≥ 2 cm in the shortest diameter that is surface accessible for CIVO injection that may be guided by ultrasound if appropriate and for which there is a planned surgical intervention. Treatment plan may include adjuvant radiation or chemotherapy, and patients should have no medical contraindication to surgery.
• Eastern Cooperative Oncology Group (ECOG) performance score 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 and one additional effective (barrier) method at the same time (see examples below) from the time of signing the informed consent form (ICF) through four months after the tumor injection procedure OR agree to completely abstain from heterosexual intercourse.
• Highly effective methods:
• Intrauterine device (IUD)
• Hormonal (birth control pills/oral contraceptives, injectable contraceptives, contraceptive patches, or contraceptive implants
• Other effective methods (barrier methods):
• Latex condom

You may not qualify if:

• Tumors 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 injection due to size, location, necrosis, cysts, excessive stroma, or fibrosis.
• 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 β-human chorionic gonadotropin (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.
• Patients with active autoimmune diseases requiring treatment or a known history of uncontrolled autoimmune disorders.
• Patients with known HIV/AIDS with uncontrolled viral load and cluster of differentiation 4 (CD4) less than 200, a known history of other relevant congenital or acquired immunodeficiencies, or known chronic hepatitis B/C.
• Patients that have received a live 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. 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 with prior treatment with other stimulator of interferon genes (STING) agonist/antagonist and toll-like receptor (TLR) agonists, or cell therapies within 2 months of the baseline/screening visit.

Sponsors & Collaborators

• Presage Biosciences: lead
• Takeda: collaborator

Study Sites (4)

LSU Health Sciences Center - Shreveport

Shreveport, Louisiana, 71115, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of Cincinnati Health

Cincinnati, Ohio, 45267, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (5)

• 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

Carboplatin; Fluorouracil; Paclitaxel; CP protocol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Wendy Jenkins

  Presage Biosciences Clinical Development

  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 substudy is not blinded. This is a cohort substudy of a Master Protocol (PBI-MST-01, NCT 04541108) framework that describes the experimental workflow for use of the CIVO platform. Comparisons will not be made between substudy cohorts.

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 2, 2023
• Study Start: July 26, 2021
• Primary Completion: November 15, 2022
• Study Completion: November 15, 2022
• Last Updated: October 6, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)