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A Study to Evaluate the Safety and Effectiveness of ILIxadencel Administered Into Tumors in Combination With Checkpoint Inhibitor (CPI) in Patients With ADvanced Cancer

NCT03735290

Description:

Patients in the Phase 1b part of the study will be treated with ilixadencel at an increasing dose and frequency, in combination with standard doses and schedules of checkpoint inhibitor (CPI) pembrolizumab. The Phase 1b study will determine the optimal dose and schedule of ilixadencel. Patients in the Phase 2 part of the study will be randomly assigned to receive either ilixadencel (at the dose determined in Phase 1b) combined with the CPI, or only the CPI.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety and Effectiveness of ILIxadencel Administered Into Tumors in Combination With Checkpoint Inhibitor (CPI) in Patients With ADvanced Cancer
  • Official Title: A Randomized, Open-label, Multi-center, Phase 1b/2 Trial Evaluating the Safety and Efficacy of Intratumorally-administered Ilixadencel in Combination With Checkpoint Inhibitor (CPI) in Advanced Cancer Subjects Who Are Candidates for CPI Therapy

Clinical Trial IDs

  • ORG STUDY ID: IM-202
  • NCT ID: NCT03735290

Conditions

  • Carcinoma, Squamous Cell of Head and Neck
  • Carcinoma, Non-Small-Cell Lung
  • Gastric Adenocarcinoma
  • Gastroesophageal Junction Adenocarcinoma
  • Non-small Cell Lung Cancer
  • Human Papilloma Virus

Interventions

DrugSynonymsArms
ilixadencelPhase 1b: Cohort 1, ilixadencel + pembrolizumab
PembrolizumabPhase 1b: Cohort 1, ilixadencel + pembrolizumab

Purpose

Patients in the Phase 1b part of the study will be treated with ilixadencel at an increasing dose and frequency, in combination with standard doses and schedules of checkpoint inhibitor (CPI) pembrolizumab. The Phase 1b study will determine the optimal dose and schedule of ilixadencel. Patients in the Phase 2 part of the study will be randomly assigned to receive either ilixadencel (at the dose determined in Phase 1b) combined with the CPI, or only the CPI.

Detailed Description

      Despite improvements achieved with the use of CPIs, 50-80% of cancer patients do not respond
      to this therapy. There is growing evidence that combining CPIs with other forms of
      immunotherapy has the potential to improve the desired effects of both CPIs and
      immunotherapies. This study looks at the safety and effectiveness of the immunotherapy
      ilixadencel when used in combination with a CPI. A Dose-escalation Committee (DEC) will
      monitor the study for any significant safety issues during Phase 1b.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1b: Cohort 1, ilixadencel + pembrolizumabExperimental3 x 10⁶ DCs (Dendritic Cells) of ilixadencel, 2x over 4 weeks (w). Pembrolizumab q3w
  • ilixadencel
  • Pembrolizumab
Phase 1b: Cohort 2, ilixadencel + pembrolizumabExperimental10 x 10⁶ DCs of ilixadencel, 2x over 4 weeks. Pembrolizumab I.V. q3w
  • ilixadencel
  • Pembrolizumab
Phase 1b: Cohort 3, ilixadencel + pembrolizumabExperimental10 x 10⁶ DCs of ilixadencel, 3x over 10 weeks. Pembrolizumab I.V. q3w
  • ilixadencel
  • Pembrolizumab
Phase 1b: Cohort 4, ilixadencel + pembrolizumabExperimentalIlixadencel 3 times over 11 weeks: 1st dose 20 x 10⁶ DCs ilixadencel; 2nd dose 10 x 10⁶ DCs; 3rd dose 10 x 10⁶ DCs. Pembrolizumab I.V. q3w
  • ilixadencel
  • Pembrolizumab
Phase 2 exp. cohorts HNSCC/NSCLC/Gastric/GEJExperimentalSubjects with HNSCC, NSCLC, gastric or gastroesophageal junction (GEJ) adenocarcinoma. ilixadencel administered intra-tumorally up to 3 times over 10 weeks; dose determined after Phase 1b. Pembrolizumab I.V. q3w according to currently approved doses and indications.
  • ilixadencel
  • Pembrolizumab
Phase 2 comparator cohorts HNSCC/NSCLC/Gastric/GEJActive ComparatorSubjects with HNSCC, NSCLC, gastric/GEJ adenocarcinoma receiving active treatment with pembrolizumab I.V. q3w according to currently approved doses and indications.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Must provide written informed consent.

          -  Must have histologically confirmed and specific (Human Papilloma Virus) HPV-positive
             or HPV-negative squamous cell carcinoma of the head and neck (SCCHN), non-small-cell
             lung cancer (NSCLC) or gastric or gastroesophageal junction (GEJ) adenocarcinoma.
             Tumor histology and most recent pathology report must be in subject's medical record.
             Tumor samples and/or biopsies will not be collected as part of this study.

          -  Eligible for pembrolizumab treatment per country-specific label and per physician's
             decision.

          -  ECOG 0 or 1.

          -  Adequate organ function.

          -  Women of childbearing potential must follow contraceptive requirements; must have a
             negative pregnancy blood test at screening, and a negative blood or urine pregnancy
             test within 24 hours before each dose of ilixadencel; and must not be breastfeeding.

          -  Male subjects must agree to use condoms from screening until 90 days after the last
             dose of ilixadencel, or must have a female partner using a highly effective method of
             contraception as described above.

        Exclusion Criteria:

          -  Prior history of invasive malignancy, unless complete remission has been achieved for
             at least 3 years and no additional therapy is required except for hormonal therapy or
             bisphosphonates.

          -  Active or previously untreated brain and/or leptomeningeal metastasis.

          -  Active autoimmune disease, pneumonitis or interstitial lung disease.

          -  Certain heart conditions including, but not limited to: Congestive heart failure;
             uncontrolled hypertension; unstable angina pectoris; pericarditis; myocarditis;
             mycardial infarction 6 months prior to study.

          -  Systemic immunosuppression except for replacement therapy.

          -  Life expectancy of less than 3 months.

          -  Any prior treatment with ilixadencel or prior treatment with anticancer agents (except
             pembrolizumab or other CPI for subjects in Phase 1b) within 4 weeks of starting study
             medication.

          -  Major surgery or significant traumatic injury within 4 weeks before study start.

          -  Known infection with human immunodeficiency virus (HIV).

          -  Active tuberculosis; active infection with hepatitis B virus or hepatitis C virus;
             active infection requiring anti-infective therapy.

        Other protocol-defined inclusion/exclusion criteria could apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency of adverse events (AEs) (Phase 1b)
Time Frame:Up to Week 27
Safety Issue:
Description:Number of adverse events

Secondary Outcome Measures

Measure:Antitumor Objective Response Rate (ORR) RECIST 1.1 (Phase 1b and Phase 2)
Time Frame:Up to Week 27
Safety Issue:
Description:Antitumor activity of ilixadencel plus CPI (checkpoint inhibitor) in each tumor type, investigator and centrally assessed using RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
Measure:Antitumor Objective Response Rate (ORR) iRECIST (Phase 1b and Phase 2)
Time Frame:Up to Week 27
Safety Issue:
Description:Antitumor activity of ilixadencel plus CPI (checkpoint inhibitor) in each tumor type, investigator assessed using iRECIST (Immune Response Evaluation Criteria in Solid Tumors)
Measure:Clinical Benefit Rate (Phase 1b and Phase 2)
Time Frame:Up to Week 27
Safety Issue:
Description:Rate of complete and partial response and stable disease by investigator and centrally assessed RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
Measure:Number of circulating CD8 t-cell responses to tumor-specific or tumor-associated antigens (Phase 1b and Phase 2)
Time Frame:Up to Week 27
Safety Issue:
Description:Measured by flow-cytometry analysis.
Measure:Duration of response (Phase 1b and Phase 2)
Time Frame:Up to 24 months after Cycle 1 Day 1
Safety Issue:
Description:Measured in weeks. Assessed using RECIST v1.1 and iRECIST
Measure:Time to Progression (TTP) (Phase 1b and Phase 2)
Time Frame:Up to 24 months after Cycle 1 Day 1
Safety Issue:
Description:Measured in weeks. Assessed using RECIST v1.1 and iRECIST
Measure:Progression-free Survival (PFS) (Phase 1b and Phase 2)
Time Frame:Up to 24 months after Cycle 1 Day 1
Safety Issue:
Description:Measured in weeks. Centrally assessed using RECIST v1.1
Measure:Overall Survival (OS) (Phase 1b and Phase 2)
Time Frame:Up to 5 years
Safety Issue:
Description:Measured in months
Measure:Frequency of adverse events (AEs) (Phase 2)
Time Frame:Up to Week 27
Safety Issue:
Description:Number of adverse events
Measure:Severity of adverse events (AEs) (Phase 2)
Time Frame:Up to Week 27
Safety Issue:
Description:Grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Measure:Number of Dose Limiting Toxicities (DLTs) (Phase 2)
Time Frame:Up to week 27
Safety Issue:
Description:Dose Limiting Toxicities measured using CTCAE v5.0 and protocol DLT definition.
Measure:Number of subjects with clinically significant laboratory test abnormalities (Phase 2)
Time Frame:Up to Week 27
Safety Issue:
Description:Grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Measure:Number of subjects with vital sign abnormalities (Phase 2)
Time Frame:Up to Week 27
Safety Issue:
Description:Vital signs grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Immunicum AB

Trial Keywords

  • immunotherapy
  • ilixadencel
  • checkpoint inhibitor
  • allogeneic
  • somatic cell therapy
  • dendritic cell
  • intratumoral
  • in situ

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