Clinical Trials /

Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC

NCT04470024

Description:

This is a phase Ib study with a safety lead-in (n = 6 per arm) evaluating combinatorial DPV-001 + sequenced PD-1 blockade, with or without GITR agonist, in recurrent or metastatic HNSCC.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC
  • Official Title: A Phase Ib Study of Multivalent Autophagosome Vaccine, With or Without GITR Agonist, With Sequenced Checkpoint Inhibition (Anti-PD-1) - Immunotherapy Trio in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Clinical Trial IDs

  • ORG STUDY ID: 2020000480
  • NCT ID: NCT04470024

Conditions

  • Cancer of the Head and Neck

Interventions

DrugSynonymsArms
INCAGN01876Arm 2
INCMGA00012Arm 1
DPV-001Arm 1

Purpose

This is a phase Ib study with a safety lead-in (n = 6 per arm) evaluating combinatorial DPV-001 + sequenced PD-1 blockade, with or without GITR agonist, in recurrent or metastatic HNSCC.

Detailed Description

      This is a phase Ib trial of an autophagosome vaccine (DPV-001) with or without anti-GITR
      (INCAGN01876), combined with subsequent anti-PD1 (INCMGA00012), in patients with recurrent or
      metastatic HNSCC. Eligible patients will be registered and assigned to one of two treatment
      arms. Subjects in Arm 1 will receive combination therapy with DPV-001 with delayed anti-PD-1,
      and subjects in Arm 2 will receive DPV-001 and anti-GITR with delayed anti-PD-1 (triplet
      therapy). Mandatory biopsy will occur at week 2. Initial restaging CT and mandatory biopsy
      will occur at 8 weeks, followed by confirmatory CT at 12 weeks. Subsequent restaging CT will
      be performed at week 24 and every 12 weeks thereafter. Starting at week 22, dosing of DPV-101
      will switch to a q4wk schedule, while the schedule of anti-GITR and anti-PD1 will remain
      unchanged.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalVax + delayed anti-PD-1
  • INCMGA00012
  • DPV-001
Arm 2ExperimentalVax + anti-GITR + delayed anti-PD-1
  • INCAGN01876
  • INCMGA00012
  • DPV-001

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Appendix C)

          -  Age 18 years or above.

          -  Laboratory values:

          -  WBC ≥2000/uL

          -  Hgb >8.0 g/dl (patients may be transfused to reach this level)

          -  Platelets >75,000 cells/mm3

          -  Serum creatinine clearance ≥ 50 mL/min measured or calculated by Cockcroft-Gault (C-G)
             equation

          -  Negative bHCG (urine/serum) Women of childbearing potential only

          -  AST (SGOT) and ALT (SGPT) ≤2.5 × upper limit of laboratory normal (ULN) OR ≤ 5 × ULN
             for participants with liver metastases

          -  Alkaline phosphatase ≤2.5 × ULN OR ≤ 5 × ULN for participants with liver metastases

          -  Total bilirubin ≤1.5 × ULN. If total bilirubin is >1.5, conjugated bilirubin must be ≤
             ULN (conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN). If
             there is no institutional ULN, then conjugated bilirubin must be < 40% of total
             bilirubin.

          -  Patients positive for hepatitis B core antibody (anti-HBc, total), are eligible only
             if HBV DNA is non-detectable by qPCR.

          -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if HCV RNA is
             non-detectable by qPCR.

          -  Patients positive for HIV 1/2 antibodies, are eligible if ARV treatment compliant with
             documented stable CD4 > 300 for at least 6 months and undetectable viral load

          -  Ability to give informed consent and comply with the protocol.

          -  Anticipated lifespan greater than 12 weeks.

          -  Women of childbearing potential must have negative serum/urine pregnancy test <5 days
             prior to start of study.

          -  Males and women of childbearing potential, must agree to take appropriate precautions
             to avoid pregnancy during treatment and through 180 days after last dose of study
             treatment (see Appendix A).

        Exclusion Criteria:

          -  Concurrent enrollment in another clinical study, unless it is an observational
             (non-interventional) clinical study or during the follow-up period of an
             interventional study.

          -  Receipt of any investigational anticancer therapy during the last 28 days or 5
             half-lives, whichever is shorter, prior to the first dose of study treatment.

          -  Any concurrent chemotherapy, investigational agent, biologic, or hormonal therapy for
             cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions
             (e.g., hormone replacement therapy) is acceptable.

          -  Local treatment of isolated lesions for palliative intent is acceptable (e.g., local
             surgery or radiotherapy), excluding target lesions, Palliative radiation therapy
             cannot be administered less than 1 week prior to the first dose of study treatment.

          -  Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
             radiation within 4 weeks of the first dose of study drug.

          -  Radiation therapy in the thoracic region that is > 30 Gy within 6 months of the first
             dose of study treatment. Note: Participants must have recovered from all
             radiation-related toxicities, not require corticosteroids for this purpose, and not
             have had radiation pneumonitis.

          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the
             first dose of study treatment. Note: Local surgery of isolated lesions for palliative
             intent is acceptable.

          -  History of organ transplant, including allogeneic stem cell transplantation.

          -  Uncontrolled intercurrent illness as deemed by the investigator, including but not
             limited to, ongoing or active infection, symptomatic congestive heart failure,
             uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia,
             interstitial lung disease or history of, serious chronic gastrointestinal conditions
             associated with diarrhea, active noninfectious pneumonitis, or psychiatric
             illness/social situations that would limit compliance with study requirement,
             substantially increase risk of incurring AEs or compromise the ability of the patient
             to give written informed consent.

          -  History of another primary malignancy except for:

               -  Malignancy treated with curative intent and with no known active disease ≥1.5
                  years before the first dose of investigational product and of low potential risk
                  for recurrence

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of disease

          -  History of leptomeningeal carcinomatosis

          -  Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
             Patients whose brain metastases have been treated may participate provided they show
             radiographic stability (imaging at least four weeks apart showing no evidence of
             intracranial progression). In addition, any neurologic symptoms that developed either
             as a result of the brain metastases or their treatment must have resolved or be stable
             either, without the use of steroids, or are stable on a steroid dose of ≤10mg/day of
             prednisone or its equivalent and anti-seizure medications for at least 14 days prior
             to the start of treatment. Patients on a stable dose of seizure medicines for epilepsy
             unrelated to cancer are eligible for the trial.

          -  History of active primary immunodeficiency.

          -  Active tuberculosis infection (clinical evaluation that includes clinical history,
             physical examination and radiographic findings, and TB testing in line with local
             practice).

          -  Active autoimmune disease requiring systemic immunosuppression in excess of
             physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or
             equivalent).:

               -  Physiologic corticosteroid replacement therapy at doses > 10 mg/day of prednisone
                  or equivalent for adrenal or pituitary insufficiency and in the absence of active
                  autoimmune disease is permitted.

               -  Participants with asthma that requires intermittent use of bronchodilators,
                  inhaled steroids, or local steroid injections may participate.

               -  Participants using topical, ocular, intra-articular, or intranasal steroids (with
                  minimal systemic absorption) may participate.

               -  Brief courses of corticosteroids for prophylaxis (eg, contrast dye allergy) or
                  study treatment-related standard premedication are permitted.

          -  Receipt of live attenuated vaccine within 28 days prior to the first dose of study
             treatment. Note: patients should not receive live vaccine during study treatment and
             up to 30 days after the last dose of study treatment.

          -  Known allergy or hypersensitivity to study drug(s) or compounds of similar biologic
             composition to the study drug(s), or any of the study drug excipients.

          -  Any unresolved NCI CTCAE Grade ≥2 toxicities from prior anti-cancer therapy with the
             exception of vitiligo, alopecia, and the laboratory values defined in the inclusion
             criteria.

          -  Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after
             consultation with the Principal Investigator or one of the Co-Principal Investigators.

          -  Patients with irreversible toxicity not reasonably expected to be exacerbated by study
             treatment may be included only after consultation with the Principal Investigator or
             one of the Co-Principal Investigators.

          -  Immune-related toxicity during prior checkpoint inhibitor therapy for which permanent
             discontinuation of therapy is recommended (per product label or consensus guidelines)
             OR

          -  any immune-related toxicity requiring intensive or prolonged immunosuppression to
             manage (with the exception of endocrinopathy that is well controlled on replacement
             hormones).

          -  Receipt of systemic antibiotics ≤ 7 days prior to the first dose of study drug.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events Assessment
Time Frame:from time of informed consent through 90 days after the last study treatment
Safety Issue:
Description:frequency, duration, and severity of adverse events

Secondary Outcome Measures

Measure:ORR, DOR, DCR
Time Frame:week 12, 24, and every 12 weeks thereafter
Safety Issue:
Description:Determined by investigator assessment per RECIST v1.1
Measure:Overall survival (OS)
Time Frame:1 year, 2 years, and study completion
Safety Issue:
Description:Determined from the start of combination until death due to any cause
Measure:Duration of disease control
Time Frame:week 12, 24, and every 12 weeks thereafter
Safety Issue:
Description:Measured from first report of SD or better (per RECIST v1.1) until PD or death

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Providence Health & Services

Last Updated

July 9, 2020