IRX-2 Regimen and Durvalumab, for Incurable H&N Squamous Cell Carcinoma

NCT03381183 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: MCC-19356ESR-16-12571
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if the IRX-2 regimen and Durvalumab, will have a tolerable safety profile and will increase the intratumoral immune profile compared with the pretreatment tumors.

Conditions

Oral Cavity Squamous Cell Carcinoma; Oropharynx Squamous Cell Carcinoma; Metastatic Squamous Cell Carcinoma; Paranasal Sinus Squamous Cell Carcinoma; Hypopharynx Squamous Cell Carcinoma; Larynx Squamous Cell Carcinoma; Squamous Cell Carcinoma; Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Phase 1 - Maximum Tolerated Dose (MTD)

  MTD of combination of the IRX-2 regimen and durvalumab as outlined in treatment arm.

  Up to 12 months

Secondary Outcomes (4)

• Phase 2 - Objective Clinical Response Rate

  Up to 12 months post treatment

• Phase 2 - Progression-free Survival (PFS)

  Up to 6 months post treatment

• Median Progression-free Survival

  Up to 12 months post treatment

• Median Overall Survival (OS)

  Up to 12 months post treatment

Study Arms (2)

Phase 1 - Dose Escalation

EXPERIMENTAL

Six patients will be enrolled at Dose Level 1 with IRX-2 230 units/day in combination with cyclophosphamide and durvalumab and treated sequentially at least 1 week apart. If less than 2 out of 6 patients have DLTs in Dose Level 1, the dose will be escalated to administration of IRX-2 460 Units/day in combination with cyclophosphamide and durvalumab as Dose Level 2. If 2 of 6 patients have DLTs, stop accrual and re-evaluate. In the next safety phase, six patients at IRX-2 460 Units/day in combination with cyclophosphamide and durvalumab will be enrolled and treated sequentially (at least 1 week apart). If DLT occurs in less than 2 of 6 patients during the first 6 weeks of treatment, enrollment can continue in the dose expansion phase at Dose Level 2. If DLT is observed in 2 of 6 patients, accrual will be stopped and Dose Level 1 will resume in the dose expansion phase.

Drug: Durvalumab; Drug: IRX-2 Regimen

Phase 2 - Dose Expansion

EXPERIMENTAL

14 patients will be enrolled at the recommended dose level from the dose finding phase for a total enrollment of 20 patients; however, investigators will replace patients with any missing tumor sample collection and continue enrollment until there are at least 20 pre- and post-treatment paired tumors (i.e. minimum 2 of 3 tumors per patient). The 6 patients treated at the recommended dose in the dose finding phase of the study will be counted as a part of the dose expansion patient population,

Drug: Durvalumab; Drug: IRX-2 Regimen

Interventions

Durvalumab DRUG

Phase 1 and Phase 2: 1500 mg every 4 weeks (Q4wks).

Also known as: MEDI4736, IMFINZI

Phase 1 - Dose Escalation; Phase 2 - Dose Expansion

IRX-2 Regimen DRUG

Phase 1 and Phase 2 - Every 12 weeks - IRX-2 Regimen: Cyclophosphamide 300 mg/m\^2 - intravenously. IRX-2: 460 units daily (4 injections of 115 units).

Phase 1 - Dose Escalation; Phase 2 - Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed squamous cell carcinoma of oral cavity, oropharynx, paranasal sinuses, nasal cavity, hypopharynx, or larynx. Squamous cell carcinoma of unknown primary in cervical lymph node can be included only if p16 status is positive.
• Must have recurrent or metastatic HNSCC that is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Participants with persistent disease following radiation therapy administered with or without a chemotherapy sensitizer may also be included.
• Willing and able to give informed consent and adhere to protocol therapy; written informed consent and any locally required authorization must be obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
• At least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Adequate normal organ and marrow function as outlined in protocol documentation
• Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as outlined in Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Life expectancy of greater than 3 months.
• Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment.
• Body weight must be \> 30 Kg.
• Participants must have a mass that is accessible and safe for repeat biopsy Note: if a participant is considered to be amendable to biopsy at the time of enrollment but is then unable to undergo a post-treatment biopsy this will not be considered an ineligible subject, although the missed biopsy will still constitute a protocol deviation.

You may not qualify if:

• Prior exposure to a combination of IRX-2 regimen, and PD-1/PD-L1 inhibitors
• Radiation therapy with a curable intent within 30 days of first dose of study treatment is excluded. However, radiation therapy with a palliative intent is allowed to treat after 14 days from the last dose of radiation.
• Any medical contraindications or previous therapy that would preclude treatment with the IRX-2 Regimen and durvalumab
• Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with the IRX- regiemtn or durvalumab may be included only after consultation with the study physician.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion: Patients with vitiligo or alopecia; Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. Any chronic skin condition that does not require systemic therapy; Patients without active disease in the last 2 years may be included but only after consultation with the study physician; Patients with celiac disease controlled by diet alone.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: Intranasal, inhaled, topical steroid, or local steroid injections (e.g., intra articular injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Concomitant anticoagulation with oral anticoagulants (such as warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (such as clopidogrel) that cannot be safely stopped.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of durvalumab. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease. Patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for systemic treatments need not be excluded.
• Myocardial infarction within the last 3 months.
• Known infection with hepatitis B, hepatitis C, or HIV.
• Signs or symptoms of systemic bacterial infection (use of antibiotics to treat superficial infection or contamination of tumor shall not, by itself, be considered evidence of infection).
• Clinically significant gastritis or peptic ulcer disease.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Brooklyn ImmunoTherapeutics, LLC: collaborator
• AstraZeneca: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Park R, Li J, Slebos RJC, Chaudhary R, Poole MI, Ferraris C, Farinhas J, Hernandez-Prera J, Kirtane K, Teer JK, Song X, Hall MS, Tasoulas J, Amelio AL, Chung CH. Phase Ib trial of IRX-2 plus durvalumab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Oral Oncol. 2024 Jul;154:106866. doi: 10.1016/j.oraloncology.2024.106866. Epub 2024 May 30.

  PMID: 38820888 DERIVED

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

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

Interventions

durvalumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Christine Chung, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 21, 2017
• Study Start: August 21, 2019
• Primary Completion: May 12, 2022
• Study Completion: June 30, 2023
• Last Updated: December 5, 2025

Record last verified: 2025-12

Locations

US (1)