Intratumoral Microdosing of TAK-981 in Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

Evaluation of TAK-981 and TAK-981 Combinations Following Intratumoral CIVO® Microdosing in Patients With Head and Neck Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04065555
• Other study ID #: PBI-TAK-01
• Status: Completed
• Phase: Early Phase 1
• Start date: October 7, 2020
• Est. completion date: July 20, 2022

Study information

• Verified date: July 2022
• Source: Presage Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

CIVO is a research tool composed of a hand-held single-use sterile injector coupled with fluorescent tracking microspheres called CIVO GLO that mark the sites of drug microdose injection, enabling rapid assessment of multiple oncology drugs or drug combinations simultaneously within a patient's tumor. In this Phase 0 intratumoral microdosing study in human patients with localized or metastatic primary tumors of the head and neck (who will be undergoing previously planned tumor and regional nodes dissection), we will evaluate TAK-981's ability to activate innate immune effector cells within the local tumor microenvironment. Additionally, this study will examine TAK-981 in combination with cetuximab or avelumab to study whether TAK-981 enhances the localized immune responses compared to those of either immunotherapy alone. TAK-981 singly and in combination with cetuximab or avelumab will be delivered intratumorally in subtherapeutic microdose quantities via CIVO. The CIVO device penetrates solid tumors and delivers subtherapeutic microdoses of up to eight anti-cancer agents or combinations of anti-cancer agents co-injected with CIVO GLO into discrete regions of the tumor. At the time of the planned surgical intervention (one or three days after the CIVO microdose injection), the injected tumor tissue is then excised and tumor responses are assessed via histological staining of tumor cross-sections sampled perpendicular to each injection column. Co-injection with CIVO GLO enables identification of each injection site during resection as well as in tissues stained for analysis. Because the platform delivers microdose amounts of each test agent or combination directly into the patient's tumor tissue, hypotheses can be tested earlier in the drug development process, consistent with the goals of the 2006 FDA Exploratory IND Guidance for Industry.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 20, 2022
• Est. primary completion date: June 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Ability and willingness to comply with the study's visit and assessment schedule.

2. Male or female = 18 years of age at Visit 1 (Screening).

3. Pathologic diagnosis of primary cancers of the head and neck.

4. 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.

5. 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.

6. ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.

7. 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.

Exclusion Criteria:

1. 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.

2. Patients who have received prior treatment with cetuximab or immune checkpoint inhibitors.

3. 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.

4. 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.

5. Patients with uncontrolled autoimmune diseases requiring treatment.

6. Patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) with uncontrolled viral load and CD4 (Cluster of Differentiation 4) less than 200.

7. Patients that have received a live vaccine within 4 weeks of the baseline/screening visit.

8. Patients with a sensitivity to Captisol.

9. Use of any of the following = 2 weeks prior to CIVO injection:

1. Immunosuppressive drugs (e.g., calcineurin inhibitors)

2. Biological response modifiers for autoimmune disease

3. 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

4. Hematopoietic growth factors

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• TAK-981
Intratumoral microdose injection by the CIVO device.

Biological:
• Cetuximab
Intratumoral microdose injection by the CIVO device.
• Avelumab
Intratumoral microdose injection by the CIVO device.

Combination Product:
• TAK-981 + Cetuximab
Intratumoral microdose injection by the CIVO device.
• TAK-981 + Avelumab
Intratumoral microdose injection by the CIVO device.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Northwell Health (Monter Cancer Center)	N. New Hyde Park	New York
United States	Northwell Health (Lenox Hill)	New York	New York
United States	Oregon Health & Science University (OHSU)	Portland	Oregon
United States	Portland VA	Portland	Oregon
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Presage Biosciences	Takeda

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Patients with Adverse Events	Relationship of AE to study drug or CIVO device will be determined using an AE Relatedness Grading System.	Up to 28 days after microdose injection

External Links

•   Presage Website