Clinical Trials /

Isunakinra Alone and in Combination With a PD-1/PD-L1 Inhibitor in Patients With Solid Tumors

NCT04121442

Description:

Isunakinra - a potent Interleukin-1 receptor inhibitor - will be given to patients with solid tumors to determine safety and tolerability of three different doses. Isunakinra will then be combined with a PD-(L)1 inhibitor. Pharmacokinetics and Pharmacodynamic effects of monotherapy treatment as well as the combination will be evaluated.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Isunakinra Alone and in Combination With a PD-1/PD-L1 Inhibitor in Patients With Solid Tumors
  • Official Title: Phase I/IIa, Non-Randomised, Open-Label Dose Escalation and Expansion Trial With Isunakinra Alone and in Combination With a PD-1/PD-L1 Inhibitor in Patients With Metastatic or Unresectable, Locally Advanced Malignant Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BUZ01CD101
  • NCT ID: NCT04121442

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
IsunakinraEBI-005Isunakinra monotherapy and in combination w PD-(L)1 Inhibitor
PD-(L)1 InhibitorIsunakinra monotherapy and in combination w PD-(L)1 Inhibitor

Purpose

Isunakinra - a potent Interleukin-1 receptor inhibitor - will be given to patients with solid tumors to determine safety and tolerability of three different doses. Isunakinra will then be combined with a PD-(L)1 inhibitor. Pharmacokinetics and Pharmacodynamic effects of monotherapy treatment as well as the combination will be evaluated.

Trial Arms

NameTypeDescriptionInterventions
Isunakinra monotherapy and in combination w PD-(L)1 InhibitorExperimentalPatients will receive specified dose of Isunakinra as monotherapy for three weeks, followed by combination with a PD-(L)1 inhibitor
  • Isunakinra
  • PD-(L)1 Inhibitor

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects must have:

               -  Metastatic or unresectable locally advanced malignant solid tumor.

               -  Histologic confirmation.

          2. The study patients are required to have measurable disease by radiographic criteria
             (RECIST 1.1) and irRC.

          3. Prior therapy: Patients must have completed or had disease progression on at least one
             prior line of disease-appropriate therapy for metastatic disease (with or without PD-1
             inhibitors), with no available therapy likely to convey clinical benefit, or not be
             candidates for therapy of proven efficacy for their disease.

          4. There should be a minimum of 2 weeks from any prior chemotherapy, immunotherapy and/or
             radiation and 4 weeks washout period for immunotherapy. Patients with prostate cancer
             on hormone deprivation therapy may continue that therapy while on study.

          5. Patients must have recovered (grade 1 or baseline) from any clinically significant
             toxicity associated with prior therapy (for example, alopecia is not clinically
             significant). Typically, this approximates 3-4 weeks for patients who most recently
             received cytotoxic therapy, except for the nitrosoureas and mitomycin C, for which 6
             weeks is needed for recovery.

          6. Age ≥ 18 years. Because no dosing or adverse event data are currently available on the
             use of this agent in patients < 18 years of age, children are excluded from this study
             but will be eligible for future pediatric trials.

          7. ECOG performance status ≤ 1

          8. Patients must have normal organ and hematologic function as defined below:

               -  Serum creatinine ≤ 1.5 x upper limit of normal OR creatinine clearance and a 24-h
                  urine collection of ≥ 60 mL/min.

               -  ALT and AST ≤ 3x the upper limits of normal.

               -  Total bilirubin ≤ 1.5 x upper limit of normal OR in patients with Gilbert's
                  syndrome, a total bilirubin ≤ 3.0.

               -  Hematological eligibility parameters (within 16 days of starting therapy):

                    -  Granulocyte count ≥ 1,500/mm3

                    -  Platelet count ≥ 75.000/mm3

          9. Patients must have baseline pulse oximetry > 90% on room air.

        Exclusion Criteria:

          1. Pregnant women or women presently breast-feeding their children are excluded due to
             unknown risks to a developing fetus or infant, confirmed by negative pre-treatment
             serum pregnancy test.

          2. Concurrent treatment for cancer, with specific exceptions noted in inclusion criteria.

          3. Any significant disease that, in the opinion of the investigator, may impair the
             patient's tolerance of study treatment.

          4. Significant dementia, altered mental status, or any psychiatric condition that would
             prohibit the understanding or rendering of informed consent.

          5. Active autoimmune diseases requiring treatment. However, patients with vitiligo,
             alopecia, or clinically stable autoimmune endocrine disease who are on appropriate
             replacement therapy (if such therapy is indicated) are eligible.

          6. Concurrent use of systemic steroids, except for physiologic doses of systemic steroid
             replacement or local (topical, nasal, or inhaled) steroid use. Limited pharmacologic
             doses of systemic steroids (e.g., in patients with exacerbations of reactive airway
             disease or to prevent iv contrast allergic reaction or anaphylaxis in patients who
             have known contrast allergies) are allowed.

          7. Patients who are receiving any other investigational agents within 28 days before
             start of study treatment.

          8. Patients with untreated central nervous system metastases or local treatment of brain
             metastases within the last 6 months. Patients with stable brain metastasis for 6
             months post-intervention are eligible.

          9. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to the agents used in study.

         10. Serious or uncontrolled intercurrent illness including, but not limited to, ongoing or
             active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of
             the investigator, would limit compliance with study requirements.

         11. HIV-positive patients are ineligible because of the potential for decreased immune
             response.

         12. Patients unwilling to use adequate contraception (defined as hormonal or barrier
             method or abstinence) prior to study entry are excluded. If the patient needs to be on
             adequate contraception, contraception must start before study entry and continue for 3
             months after completion of study therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients who experience DLTs
Time Frame:From baseline to 49 days of treatment
Safety Issue:
Description:The primary endpoint of this study is the proportion of patients who experience DLTs. The MTD (Maximum Tolerated Dose) will be determined based on the dose escalation cohorts. The evaluation period for DLTs will be 21 days following the first dose of Isunakinra and 28 days following addition of PD1-PDL1 inhibitor

Secondary Outcome Measures

Measure:Percent of individuals who experience radiographic response
Time Frame:Two years
Safety Issue:
Description:Overall response rate (ORR) by RECIST 1.1
Measure:Progression-free survival (PFS)
Time Frame:Two years
Safety Issue:
Description:Defined as the time, in days, between treatment initiation and when the patient is found to have recurrent and/or metastatic disease on imaging, or death for any reason.
Measure:Overall survival
Time Frame:Two years
Safety Issue:
Description:Defined as the time, in days, between treatment initiation and when the patient dies from any cause regardless of etiology.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Buzzard Pharmaceuticals

Last Updated

October 11, 2019