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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 (ILIAD)

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ClinicalTrials.gov Identifier: NCT03735290
Recruitment Status : Not yet recruiting
First Posted : November 8, 2018
Last Update Posted : December 13, 2018
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
Immunicum AB

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Biological: ilixadencel Drug: Pembrolizumab Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Single arm phase 1b. Randomized phase 2.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1b: Cohort 1, ilixadencel + pembrolizumab
3 x 10⁶ DCs (Dendritic Cells) of ilixadencel, 2x over 4 weeks (w). Pembrolizumab q3w
Biological: ilixadencel
Intra-tumoral injection

Drug: Pembrolizumab
Administered intravenously over 30 minutes, every 3 weeks, at a dose of 200 mg

Experimental: Phase 1b: Cohort 2, ilixadencel + pembrolizumab
10 x 10⁶ DCs of ilixadencel, 2x over 4 weeks. Pembrolizumab I.V. q3w
Biological: ilixadencel
Intra-tumoral injection

Drug: Pembrolizumab
Administered intravenously over 30 minutes, every 3 weeks, at a dose of 200 mg

Experimental: Phase 1b: Cohort 3, ilixadencel + pembrolizumab
10 x 10⁶ DCs of ilixadencel, 3x over 10 weeks. Pembrolizumab I.V. q3w
Biological: ilixadencel
Intra-tumoral injection

Drug: Pembrolizumab
Administered intravenously over 30 minutes, every 3 weeks, at a dose of 200 mg

Experimental: Phase 1b: Cohort 4, ilixadencel + pembrolizumab
Ilixadencel 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
Biological: ilixadencel
Intra-tumoral injection

Drug: Pembrolizumab
Administered intravenously over 30 minutes, every 3 weeks, at a dose of 200 mg

Experimental: Phase 2 exp. cohorts HNSCC/NSCLC/Gastric/GEJ
Subjects 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.
Biological: ilixadencel
Intra-tumoral injection

Drug: Pembrolizumab
Administered intravenously over 30 minutes, every 3 weeks, at a dose of 200 mg

Active Comparator: Phase 2 comparator cohorts HNSCC/NSCLC/Gastric/GEJ
Subjects with HNSCC, NSCLC, gastric/GEJ adenocarcinoma receiving active treatment with pembrolizumab I.V. q3w according to currently approved doses and indications.
Drug: Pembrolizumab
Administered intravenously over 30 minutes, every 3 weeks, at a dose of 200 mg




Primary Outcome Measures :
  1. Frequency of adverse events (AEs) (Phase 1b) [ Time Frame: Up to Week 27 ]
    Number of adverse events

  2. Severity of adverse events (SAEs) (Phase 1b) [ Time Frame: Up to Week 27 ]
    Grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  3. Number of Dose Limiting Toxicities (DLTs) (Phase 1b) [ Time Frame: Up to Week 27 ]
    Dose Limiting Toxicities measured using CTCAE v5.0 and protocol DLT definition.

  4. Number of subjects with clinically significant laboratory test abnormalities (Phase 1b) [ Time Frame: Up to Week 27 ]
    Grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  5. Number of subjects with vital sign abnormalities (Phase 1b) [ Time Frame: Up to Week 27 ]
    Vital signs grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  6. Antitumor Objective Response Rate (ORR) (Phase 2) [ Time Frame: Up to Week 27 ]
    Antitumor activity of ilixadencel plus CPI (checkpoint inhibitor) in each tumor type, centrally assessed using RECIST (Response Evaluation Criteria in Solid Tumors) v1.1


Secondary Outcome Measures :
  1. Antitumor Objective Response Rate (ORR) RECIST 1.1 (Phase 1b and Phase 2) [ Time Frame: Up to Week 27 ]
    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

  2. Antitumor Objective Response Rate (ORR) iRECIST (Phase 1b and Phase 2) [ Time Frame: Up to Week 27 ]
    Antitumor activity of ilixadencel plus CPI (checkpoint inhibitor) in each tumor type, investigator assessed using iRECIST (Immune Response Evaluation Criteria in Solid Tumors)

  3. Clinical Benefit Rate (Phase 1b and Phase 2) [ Time Frame: Up to Week 27 ]
    Rate of complete and partial response and stable disease by investigator and centrally assessed RECIST (Response Evaluation Criteria in Solid Tumors) v1.1

  4. 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 ]
    Measured by flow-cytometry analysis.

  5. Duration of response (Phase 1b and Phase 2) [ Time Frame: Up to 24 months after Cycle 1 Day 1 ]
    Measured in weeks. Assessed using RECIST v1.1 and iRECIST

  6. Time to Progression (TTP) (Phase 1b and Phase 2) [ Time Frame: Up to 24 months after Cycle 1 Day 1 ]
    Measured in weeks. Assessed using RECIST v1.1 and iRECIST

  7. Progression-free Survival (PFS) (Phase 1b and Phase 2) [ Time Frame: Up to 24 months after Cycle 1 Day 1 ]
    Measured in weeks. Centrally assessed using RECIST v1.1

  8. Overall Survival (OS) (Phase 1b and Phase 2) [ Time Frame: Up to 5 years ]
    Measured in months

  9. Frequency of adverse events (AEs) (Phase 2) [ Time Frame: Up to Week 27 ]
    Number of adverse events

  10. Severity of adverse events (AEs) (Phase 2) [ Time Frame: Up to Week 27 ]
    Grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  11. Number of Dose Limiting Toxicities (DLTs) (Phase 2) [ Time Frame: Up to week 27 ]
    Dose Limiting Toxicities measured using CTCAE v5.0 and protocol DLT definition.

  12. Number of subjects with clinically significant laboratory test abnormalities (Phase 2) [ Time Frame: Up to Week 27 ]
    Grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  13. Number of subjects with vital sign abnormalities (Phase 2) [ Time Frame: Up to Week 27 ]
    Vital signs grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03735290


Contacts
Contact: Dan Campbell +1 910-558-8815 ImmunicumClinicalTrial.sm@ppdi.com

Locations
United States, Kentucky
Site 1011 Not yet recruiting
Louisville, Kentucky, United States, 40065
Contact: Please email ImmunicumClinicalTrial@ppdi.com. First line of the email MUST contain NCT# and Site #.       ImmunicumClinicalTrial.sm@ppdi.com   
United States, Michigan
Site 1001 Not yet recruiting
Detroit, Michigan, United States, 48202
Contact: Please email ImmunicumClinicalTrial@ppdi.com. First line of the email MUST contain NCT# and Site #.       ImmunicumClinicalTrial.sm@ppdi.com   
Sponsors and Collaborators
Immunicum AB
PPD
Investigators
Study Director: Peter Suenaert, MD, PhD Immunicum AB

Additional Information:
Responsible Party: Immunicum AB
ClinicalTrials.gov Identifier: NCT03735290     History of Changes
Other Study ID Numbers: IM-202
First Posted: November 8, 2018    Key Record Dates
Last Update Posted: December 13, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Immunicum AB:
immunotherapy
ilixadencel
checkpoint inhibitor
allogeneic
somatic cell therapy
dendritic cell
intratumoral
in situ

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Papilloma
Esophageal Neoplasms
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Pembrolizumab
Antineoplastic Agents