Clinical trial NCT03735290: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Carcinoma, Squamous Cell of Head and Neck
Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Non-small Cell Lung Cancer
Keywords: immunotherapy
ilixadencel
checkpoint inhibitor
allogeneic
somatic cell therapy
dendritic cell
intratumoral
in situ
Lead sponsor: Mendus
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
First posted: 2018-11-08
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Single arm phase 1b. Randomized phase 2.
Primary purpose: TREATMENT

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.

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

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.

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. 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.

Primary outcomes:
measure: Frequency of adverse events (AEs) (Phase 1b)
timeFrame: Up to Week 27
measure: Severity of adverse events (AEs) (Phase 1b)
timeFrame: Up to Week 27
measure: Number of Dose Limiting Toxicities (DLTs) (Phase 1b)
timeFrame: Up to Week 27
measure: Number of subjects with clinically significant laboratory test abnormalities (Phase 1b)
timeFrame: Up to Week 27
measure: Number of subjects with vital sign abnormalities (Phase 1b)
timeFrame: Up to Week 27
measure: Antitumor Objective Response Rate (ORR) (Phase 2)
timeFrame: Up to Week 27
Secondary outcomes:
measure: Antitumor Objective Response Rate (ORR) RECIST 1.1 (Phase 1b and Phase 2)
timeFrame: Up to Week 27
measure: Antitumor Objective Response Rate (ORR) iRECIST (Phase 1b and Phase 2)
timeFrame: Up to Week 27
measure: Clinical Benefit Rate (Phase 1b and Phase 2)
timeFrame: Up to Week 27
measure: Duration of response (Phase 1b and Phase 2)
timeFrame: Up to 24 months after Cycle 1 Day 1
measure: Time to Progression (TTP) (Phase 1b and Phase 2)
timeFrame: Up to 24 months after Cycle 1 Day 1
measure: Progression-free Survival (PFS) (Phase 1b and Phase 2)
timeFrame: Up to 24 months after Cycle 1 Day 1
measure: Overall Survival (OS) (Phase 1b and Phase 2)
timeFrame: Up to 5 years
measure: Frequency of adverse events (AEs) (Phase 2)
timeFrame: Up to Week 27
measure: Severity of adverse events (AEs) (Phase 2)
timeFrame: Up to Week 27
measure: Number of Dose Limiting Toxicities (DLTs) (Phase 2)
timeFrame: Up to week 27
measure: Number of subjects with clinically significant laboratory test abnormalities (Phase 2)
timeFrame: Up to Week 27
measure: Number of subjects with vital sign abnormalities (Phase 2)
timeFrame: Up to Week 27
Other outcomes:
Locations:
city: Coral Gables
country: United States
facility: Site 1010
state: Florida
city: Iowa City
country: United States
facility: Site 1006
state: Iowa
city: Louisville
country: United States
facility: Site 1011
state: Kentucky
city: Chapel Hill
country: United States
facility: Site 1004
state: North Carolina
city: Cleveland
country: United States
facility: Site 1009
state: Ohio
Study officials:
affiliation: Mendus
name: Petra Domeij
role: STUDY_DIRECTOR
References: