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

Head and Neck Squamous Cell Carcinoma Clinical Trial

Official title:

A Phase 0 Multicenter Study of the Pharmacodynamic Effects of Intratumoral Microdose Administration of Rilvegostomig, Volrustomig, and Sabestomig

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06366451
• Other study ID #: MST01-AZN-05
• Secondary ID: PBI-MST-01
• Status: Recruiting
• Phase: Early Phase 1
• Start date: April 2024
• Est. completion date: March 2025

Study information

• Verified date: April 2024
• Source: Presage Biosciences
• Contact: Presage Biosciences
• Phone: 800-530-5404
• Email: clinops[@]presagebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, open-label, Phase 0 substudy designed to evaluate the localized pharmacodynamics (PD) of rilvegostomig, volrustomig, and sabestomig 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 will be compared to those elicited by pembrolizumab alone, which will also be injected in microdose quantities via the CIVO device.

Description:

The CIVO Microdose Injection Device (MID) simultaneously delivers multiple drugs and drug combinations (Up to 8), each in microdose amounts, into a single patient tumor and enables comparisons of the resulting biomarker responses that occurred while that tumor was still in the native microenvironment. AstraZeneca is developing three novel assets: rilvegostomig, volrustomig, and sabestomig, all of which are bispecific monoclonal antibodies designed to stimulate antitumor immunity. In this Phase 0 clinical trial, the PD effects of these investigational assets in the TME of patients presenting with HNSCC will be evaluated. These investigational assets will be injected alone in microdose quantities at tumor sites in HNSCC patients. Pembrolizumab, also used therapeutically in this patient population, will be included in the CIVO injection array administered as a single agent. The CIVO-injected portion of the tissue will be analyzed for localized response at sites of drug exposure in the TME.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

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

3. Pathologic diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC) of the oropharynx, hypopharynx, oral cavity, or larynx.

4. Ability and willingness to comply with the study's visits and assessment schedule.

5. 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.

6. Eastern Cooperative Oncology Group (ECOG) 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
• 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 150 days 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 150 days after the CIVO injection.
• Agree to refrain from breastfeeding until 150 days after the CIVO injection.

8. 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 150 days after the CIVO injection OR agree to completely abstain from heterosexual intercourse.
• Agree to refrain from fathering a child or donating sperm until 150 days after the CIVO injection.

Exclusion Criteria:

1. 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.

2. Tumors near or involving critical structures for which, in the opinion of the treating clinician, injection would pose undue risk to the patient.

3. 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.

4. Patients with concurrent cancer, immune disease or active infection requiring systemic or radiotherapy.

5. 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.

6. 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.

7. History of organ transplant.

8. Major surgery within 4 weeks prior to injection: subject must have adequate wound healing and have recovered from any prior surgery.

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Biological:
• Rilvegostomig
Intratumoral microdose injection by the CIVO device.
• Volrustomig
Intratumoral microdose injection by the CIVO device.
• Sabestomig
Intratumoral microdose injection by the CIVO device.
• Pembrolizumab
Intratumoral microdose injection by the CIVO device.

Locations

Country	Name	City	State
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Sarah Cannon Medical Center	Charleston	South Carolina
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University (OHSU)	Portland	Oregon
United States	UC Davis	Sacramento	California
United States	LSU Health Sciences Center - Shreveport	Shreveport	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Presage Biosciences	AstraZeneca

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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	Evaluation of signature scores using Gene Set Variability Analysis within regions injected with microdoses of rilvegostomig, volrustomig, sabestomig, or pembrolizumab	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 or ISH technique.	1 to 3 days after microdose injection
Secondary	Incidence of reported Adverse Events and/or Adverse Device Effects [Safety and Tolerability]	Safety of the microdose injection procedure and injected content will be assessed by quantification of the frequency, intensity, and relatedness of all reported Adverse Events and/or Adverse Device Effects.	Up to 28 days after microdose injection