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 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: IM-202
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (12)

• Antitumor Objective Response Rate (ORR) RECIST 1.1 (Phase 1b and Phase 2)

  Up to Week 27

• Antitumor Objective Response Rate (ORR) iRECIST (Phase 1b and Phase 2)

  Up to Week 27

• Clinical Benefit Rate (Phase 1b and Phase 2)

  Up to Week 27

• Duration of response (Phase 1b and Phase 2)

  Up to 24 months after Cycle 1 Day 1

• Time to Progression (TTP) (Phase 1b and Phase 2)

  Up to 24 months after Cycle 1 Day 1

Study Arms (6)

Phase 1b: Cohort 1, ilixadencel + pembrolizumab

EXPERIMENTAL

3 x 10⁶ DCs (Dendritic Cells) of ilixadencel, 2x over 4 weeks (w). Pembrolizumab I.V. q3w

Biological: ilixadencel; Drug: Pembrolizumab

Phase 1b: Cohort 2, ilixadencel + pembrolizumab

EXPERIMENTAL

10 x 10⁶ DCs of ilixadencel, 2x over 4 weeks. Pembrolizumab I.V. q3w

Biological: ilixadencel; Drug: Pembrolizumab

Phase 1b: Cohort 3, ilixadencel + pembrolizumab

EXPERIMENTAL

10 x 10⁶ DCs of ilixadencel, 3x over 10 weeks. Pembrolizumab I.V. q3w

Biological: ilixadencel; Drug: Pembrolizumab

Phase 1b: Cohort 4, ilixadencel + pembrolizumab

EXPERIMENTAL

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; Drug: Pembrolizumab

Phase 2 exp. cohorts HNSCC/NSCLC/Gastric/GEJ

EXPERIMENTAL

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; Drug: Pembrolizumab

Phase 2 comparator cohorts HNSCC/NSCLC/Gastric/GEJ

ACTIVE COMPARATOR

Subjects with HNSCC, NSCLC, gastric/GEJ adenocarcinoma receiving active treatment with pembrolizumab I.V. q3w according to currently approved doses and indications.

Drug: Pembrolizumab

Interventions

ilixadencel BIOLOGICAL

Intra-tumoral injection

Phase 1b: Cohort 1, ilixadencel + pembrolizumab; Phase 1b: Cohort 2, ilixadencel + pembrolizumab; Phase 1b: Cohort 3, ilixadencel + pembrolizumab; Phase 1b: Cohort 4, ilixadencel + pembrolizumab; Phase 2 exp. cohorts HNSCC/NSCLC/Gastric/GEJ

Pembrolizumab DRUG

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

Phase 1b: Cohort 1, ilixadencel + pembrolizumab; Phase 1b: Cohort 2, ilixadencel + pembrolizumab; Phase 1b: Cohort 3, ilixadencel + pembrolizumab; Phase 1b: Cohort 4, ilixadencel + pembrolizumab; Phase 2 comparator cohorts HNSCC/NSCLC/Gastric/GEJ; Phase 2 exp. cohorts HNSCC/NSCLC/Gastric/GEJ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must provide written informed consent.
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Mendus: lead
• PPD Development, LP: collaborator

Study Sites (5)

Site 1010

Coral Gables, Florida, 33124, United States

Location

Site 1006

Iowa City, Iowa, 52242, United States

Location

Site 1011

Louisville, Kentucky, 40202, United States

Location

Site 1004

Chapel Hill, North Carolina, 27514, United States

Location

Site 1009

Cleveland, Ohio, 44106, United States

Location

Related Links

• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Petra Domeij

  Mendus

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm phase 1b. Randomized phase 2.

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: November 8, 2018
• Study Start: January 14, 2019
• Primary Completion: December 3, 2021
• Study Completion: December 3, 2021
• Last Updated: March 16, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)