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

Non-small Cell Lung Cancer Clinical Trial

— ILIAD  

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03735290
• Other study ID #: IM-202
• Status: Terminated
• Phase: Phase 1
• Start date: January 14, 2019
• Est. completion date: December 3, 2021

Study information

• Verified date: March 2022
• Source: Immunicum AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: December 3, 2021
• Est. primary completion date: December 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Biological:
• ilixadencel
Intra-tumoral injection

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

Locations

Country	Name	City	State
United States	Site 1004	Chapel Hill	North Carolina
United States	Site 1009	Cleveland	Ohio
United States	Site 1010	Coral Gables	Florida
United States	Site 1006	Iowa City	Iowa
United States	Site 1011	Louisville	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Immunicum AB	PPD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse events (AEs) (Phase 1b)	Number of adverse events	Up to Week 27
Primary	Severity of adverse events (AEs) (Phase 1b)	Grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Up to Week 27
Primary	Number of Dose Limiting Toxicities (DLTs) (Phase 1b)	Dose Limiting Toxicities measured using CTCAE v5.0 and protocol DLT definition.	Up to Week 27
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall Survival (OS) (Phase 1b and Phase 2)	Measured in months	Up to 5 years
Secondary	Frequency of adverse events (AEs) (Phase 2)	Number of adverse events	Up to Week 27
Secondary	Severity of adverse events (AEs) (Phase 2)	Grading per Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Up to Week 27
Secondary	Number of Dose Limiting Toxicities (DLTs) (Phase 2)	Dose Limiting Toxicities measured using CTCAE v5.0 and protocol DLT definition.	Up to week 27
Secondary	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
Secondary	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

External Links

•   FDA Safety Alerts and Recalls