AMD3100 Plus Pembrolizumab in Immune Checkpoint Blockade Refractory Head and Neck Squamous Cell Carcinoma

NCT04058145 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 19-189
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This research is studying the safety and effectiveness of AMD3100 and pembrolizumab in participants with metastatic head and neck squamous cell carcinoma.

Conditions

Head and Neck Cancer

Keywords

Head and Neck Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants That Experience a Dose Limiting Toxicity

  A safety run in will be conducted with AMD3100 administered weekly or every three weeks, both in combination with pembrolizumab administered every three weeks. The number of participants that experience dose limiting toxicities will be reported for each arm.

  From the start of treatment up to 24 months, or until disease progression or intolerable toxicity, whichever occurs first

• Overall Response Rate

  Overall response rate will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST). A participant is considered to have achieved a response if the achieve either of the following: * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters

  From the start of treatment up to 24 months, or until disease progression or intolerable toxicity, whichever occurs first

Secondary Outcomes (4)

• Progression Free Survival

  From the time of randomization until disease progression or death, up to approximately 5 years

• Overall Survival

  From the time of randomization until death, up to approximately 5 years

• The Number of Participants With Treatment-Related Serious Adverse Events

  From the start of treatment until 30 days after the end of treatment, up to 25 months

• Duration of Response

  From the time of first response until disease progression, up to 24 months

Study Arms (3)

Pembrolizumab+AMD3100 q3w

EXPERIMENTAL

* Pembrolizumab is administered intravenously on day 1 of each cycle * AMD3 100 is administered via injection subcutaneously on day 1 of each cycle

Drug: AMD3100; Drug: Pembrolizumab

Pembrolizumab+AMD3100 weekly

EXPERIMENTAL

* Pembrolizumab is administered intravenously on day 1 of each cycle * AMD3 100 is administered via injection subcutaneously on a weekly basis

Drug: AMD3100; Drug: Pembrolizumab

Pembrolizumab+AMD3100

EXPERIMENTAL

* Pembrolizumab is administered intravenously * AMD3 100 is administered via injection subcutaneously

Drug: AMD3100; Drug: Pembrolizumab

Interventions

AMD3100 DRUG

AMD3100 is a drug that inhibits a chemokine CXCR4 which promotes cancer cell growth, spread, and survival and controls immune cell trafficking. Inhibiting CXCR4 expels the immune-suppressive cells out of the tumor and attract the cancer-killing immune cells into the tumor environment so that the body's immune system may be able to better attack the cancer cells.

Also known as: Plerixafor

Pembrolizumab+AMD3100; Pembrolizumab+AMD3100 q3w; Pembrolizumab+AMD3100 weekly

Pembrolizumab DRUG

Pembrolizumab is thought to block a receptor called PD-1. This receptor usually acts as a "brake" to prevent the body's immune system from attacking cancer cells. The antibody "removes the brake" to allow parts of the body's immune system (usually T cells) to attack the tumor.

Also known as: Keytruda

Pembrolizumab+AMD3100; Pembrolizumab+AMD3100 q3w; Pembrolizumab+AMD3100 weekly

Eligibility Criteria

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

You may qualify if:

• Have histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the recurrent or metastatic head and neck. For oropharyngeal cancer, tumor HPV status must be known.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Have progressed on or after immune checkpoint therapy (anti-PD-1 or anti-PD-L1, as a monotherapy or in combination with other agents). Anti-PD-1/PD-L1 immune checkpoint therapy does not have to be the most immediate prior therapy before the study enrollment.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. If slides are to be submitted, 10-20 unstained slides are required. Newly obtained biopsies are preferred to archived tissue. At a minimum, 3 core biopsies will be obtained and 1 core will be formalin fixed and the other 2 cores will be flash frozen.
• Have a lesion that is accessible for biopsy for subjects in the Run-In phase. An exception can be granted for those patients who do not have a lesion that can be safely biopsied based upon review with the Principal Investigator. The tumor biopsy is optional in the Phase II portion of the study
• Be \>18 years of age on the day of signing informed consent.
• ECOG performance status ≤ 1 (Karnofsky ≥70%, see Appendix A).
• Have normal organ and marrow function as defined below. Specimens must be collected within 28 days prior to study registration.
• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤1.5 ×ULN
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
• creatinine Within normal institutional limits, OR
• creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.

You may not qualify if:

• Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to registration with the exception of receiving immune checkpoint blockade therapy.
• Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible after discussion with PI.
• Has received prior radiotherapy within 2 weeks of first dose of study drug.
• Participants must have recovered from all radiation-related toxicities to ≤Grade 1 or baseline, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 2 weeks prior to the first dose of study drug. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been \>2 weeks since the last dose of the previous investigational agent.
• Has a known diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab, AMD3100, and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV).
• No HIV testing is required unless mandated by local health authority.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Merck Sharp & Dohme LLC: collaborator
• AperiSys, Inc: collaborator

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02062, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

plerixafor; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Officials

• Jong Chul Park, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: August 15, 2019
• Study Start: September 30, 2019
• Primary Completion: October 11, 2019
• Study Completion: October 11, 2019
• Last Updated: September 7, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)