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)

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

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.

Note: Recruitment to Phase 1b of the study has been completed.

Study Overview

• Status: Terminated
• Conditions: Gastric Adenocarcinoma; Non-small Cell Lung Cancer; Gastroesophageal Junction Adenocarcinoma; Carcinoma, Squamous Cell of Head and Neck
• Intervention / Treatment: Biological: ilixadencel; Drug: Pembrolizumab

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.

Note: Recruitment to Phase 1b of the study has been completed.

The study did not move forward to Phase 2.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Coral Gables, Florida, United States, 33124
      • Site 1010
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Site 1006
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Site 1011
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Site 1004
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Site 1009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. Patients with other tumor types who are candidates for pembrolizumab therapy (according to the FDA-approved prescribing information at the time of inclusion) can also be enrolled in Phase 1b. 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 (Eastern Cooperative Oncology Group) performance status of 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 requiring anti-infective therapy (hepatitis with a negative viral load on maintenance will not be excluded).

Other protocol-defined inclusion/exclusion criteria could apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Phase 1b: Cohort 1, ilixadencel + pembrolizumab; 3 x 10⁶ DCs (Dendritic Cells) of ilixadencel, 2x over 4 weeks (w). 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 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 10 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events (AEs) (Phase 1b)	Number of adverse events	Up to Week 27
Severity of adverse events (AEs) (Phase 1b)	Grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Up to Week 27
Number of Dose Limiting Toxicities (DLTs) (Phase 1b)	Dose Limiting Toxicities measured using CTCAE v5.0 and protocol DLT definition.	Up to Week 27
Number of subjects with clinically significant laboratory test abnormalities (Phase 1b)	Grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Up to Week 27
Number of subjects with vital sign abnormalities (Phase 1b)	Vital signs grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Up to Week 27
Antitumor Objective Response Rate (ORR) (Phase 2)	Antitumor activity of ilixadencel plus CPI (checkpoint inhibitor) in each tumor type, centrally assessed using RECIST (Response Evaluation Criteria in Solid Tumors) v1.1	Up to Week 27

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mendus
• Collaborators: PPD
• Investigators: Study Director: Petra Domeij, Mendus

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 14, 2019
• Primary Completion (ACTUAL): December 3, 2021
• Study Completion (ACTUAL): December 3, 2021

Study Registration Dates

• First Submitted: November 7, 2018
• First Submitted That Met QC Criteria: November 7, 2018
• First Posted (ACTUAL): November 8, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 1, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: immunotherapy; checkpoint inhibitor; dendritic cell; allogeneic; in situ; somatic cell therapy; intratumoral; ilixadencel
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Adenocarcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: IM-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No