Intratumoral Microdosing of TAK-981 in Head and Neck Cancer

NCT04065555 | Completed Early Phase 1 FDA Drug

• 1 other identifier: PBI-TAK-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 6

Brief Summary

This is a multi-center, single arm, open-label, multi-agent, localized pharmacodynamic biomarker Phase 0 trial designed to study the biological effects within the tumor microenvironment of TAK-981 and TAK-981 combined with cetuximab or avelumab when administered intratumorally in microdose quantities via the CIVO device. CIVO stands for comparative in vivo oncology.

Conditions

Head and Neck Cancer

Keywords

precision oncology; intratumoral microdosing; microdose injection; microinjection; microdosing; in vivo oncology; in vivo drug sensitivity; tumor microenvironment; multiplexed immunohistochemistry; HNSCC; SCCHN

Outcome Measures

Primary Outcomes (1)

• Quantification of Cell Death and Immune Cell Biomarkers by Immunohistochemistry (IHC) and In-Situ Hybridization (ISH) in Resected Tissue

  Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumor microenvironment around each of the injection sites of each resected patient sample by IHC and ISH. An aggregate analysis of this quantification may be done across patient samples to evaluate trends in tumor response. List of biomarkers evaluated may include biomarkers for cell death (e.g. cleaved caspase 3), T-cells (e.g. CD3, CD8/Granzyme B), and natural killer (NK) or myeloid cells (e.g. CD56/Granzyme B, CD86, CD68).

  1 or 3 days after microdose injection

Secondary Outcomes (1)

• Number of Patients with Adverse Events

  Up to 28 days after microdose injection

Study Arms (1)

CIVO Microdose Injection of TAK-981, Cetuximab, and Avelumab

EXPERIMENTAL

Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected one day (Cohort 1) or three days (Cohort 2) 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-981, cetuximab, avelumab, TAK-981 combined with cetuximab, or TAK-981 combined with avelumab. 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. Approximately six patients will be assigned to each time point cohort. Cohort assignment is not sequential and will be selected by the Investigator based on clinic logistics and patient scheduling. Should one cohort fill in advance of the other, sites will be directed by Presage to enroll patients into the second cohort only.

Drug: TAK-981; Biological: Cetuximab; Biological: Avelumab; Combination Product: TAK-981 + Cetuximab; Combination Product: TAK-981 + Avelumab

Interventions

TAK-981 DRUG

Intratumoral microdose injection by the CIVO device.

CIVO Microdose Injection of TAK-981, Cetuximab, and Avelumab

Cetuximab BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: ERBITUX

CIVO Microdose Injection of TAK-981, Cetuximab, and Avelumab

Avelumab BIOLOGICAL

Intratumoral microdose injection by the CIVO device.

Also known as: Bavencio

CIVO Microdose Injection of TAK-981, Cetuximab, and Avelumab

TAK-981 + Cetuximab COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

Also known as: TAK-981 + ERBITUX

CIVO Microdose Injection of TAK-981, Cetuximab, and Avelumab

TAK-981 + Avelumab COMBINATION_PRODUCT

Intratumoral microdose injection by the CIVO device.

Also known as: TAK-981 + Bavencio

CIVO Microdose Injection of TAK-981, Cetuximab, and Avelumab

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 primary cancers of the head and neck.
• 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 must have no medical contraindication to surgery.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.
• Female patients who:
• Are postmenopausal for at least one year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice two effective methods of contraception, at the same time, from the time of signing of the informed consent through four months 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 during the entire study treatment period through four months after the tumor injection procedure, OR
• Agree to completely abstain from heterosexual intercourse.
• Agree to refrain from donating sperm during study participation.

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, fibrosis, or treatment-induced tissue changes. Lesions that have received neoadjuvant radiation therapy may lack sufficient viable tumor tissue for CIVO injection procedures.
• Patients who have received prior treatment with cetuximab or immune checkpoint inhibitors.
• Female patients who are both lactating and breastfeeding or have a positive serum pregnancy during the screening period or a positive urine pregnancy test on Day 1 before the tumor injection procedure.
• 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 uncontrolled autoimmune diseases requiring treatment.
• Patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) with uncontrolled viral load and CD4 (Cluster of Differentiation 4) less than 200.
• Patients that have received a live vaccine within 4 weeks of the baseline/screening visit.
• Patients with a sensitivity to Captisol.
• Use of any of the following ≤ 2 weeks prior to CIVO injection:
• Immunosuppressive drugs (e.g., calcineurin inhibitors)
• Biological response modifiers for autoimmune disease
• Systemic glucocorticoids: oral or parenteral corticosteroids at a dose ≥ 20 mg/day prednisone, or equivalent Note: physiologic replacement dosing of steroids (≤ 3mg/m2/d prednisone or equivalent), low-dose corticosteroids for dye allergies prior to staging scans or use in anti-emetic prophylaxis for patients undergoing chemotherapy, or topical steroids, are allowed
• Hematopoietic growth factors

Sponsors & Collaborators

• Presage Biosciences: lead
• Takeda: collaborator

Study Sites (6)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Northwell Health (Lenox Hill)

New York, New York, 10075, United States

Location

Northwell Health (Monter Cancer Center)

North New Hyde Park, New York, 11042, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

Portland VA

Portland, Oregon, 97239, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Related Publications (5)

• 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

• 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

Related Links

• Presage Website

MeSH Terms

Conditions

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

Interventions

TAK-981; Cetuximab; avelumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical 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

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 22, 2019
• Study Start: October 7, 2020
• Primary Completion: June 20, 2022
• Study Completion: July 20, 2022
• Last Updated: July 29, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)