Study of Tilsotolimod in Combination With Nivolumab and Ipilimumab for the Treatment of Solid Tumors (ILLUMINATE-206)

NCT03865082 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 2125-MST-206
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

A Phase 2 study intended to see efficacy of tilsotolimod in combination with immunotherapy drugs ipilimumab and nivolumab in different solid tumors.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Demonstrate the efficacy of intratumoral tilsotolimod in combination with ipilimumab and nivolumab for each cohort

  Efficacy measure by objective response rate

  ORR defined as a CR or partial response (PR) according to RECIST v1.1, confirmed by imaging ≥ 4 weeks after the initial documentation of response (to occur up to 24 months).

• Duration of response

  Durability or response per RECIST v1.1

  DOR will be evaluated every 8 weeks starting Cycle3 Day1 (each cycle is 28 days) for year 1 then every 12 weeks after the first year through study completion until all study participants have either progressive disease or start new anticancer treatment.

Secondary Outcomes (1)

• Safety and tolerability of the combination of tilsotolimod with nivolumab and ipilimumab

  At every study visit (up to 48 months)

Study Arms (1)

IO Naive Subjects MSS CRC

EXPERIMENTAL

8mg Tilsotolimod by intratumoral injection plus 3mg/kg Nivolumab (every three weeks for four doses followed by 480mg dose every four weeks) and 1mg/kg Ipilimumab every three weeks for four doses intravenous

Drug: Tilsotolimod; Drug: Nivolumab; Drug: Ipilimumab

Interventions

Tilsotolimod DRUG

9 doses of Tilsotolimod Intratumoral injection administered as a dose of 8mg at Week 0 Day 1 (7 days prior to the start of Cycle 1), Day 1 and Day 8 of Cycle 1, and on Day 1 of Cycles 2 through 7.

Also known as: IMO-2125

IO Naive Subjects MSS CRC

Nivolumab DRUG

Specified dose on specified days.

Also known as: OPDIVO

IO Naive Subjects MSS CRC

Ipilimumab DRUG

Specified dose on specified days.

Also known as: Yervoy

IO Naive Subjects MSS CRC

Eligibility Criteria

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

You may qualify if:

• Subject must be willing and able to sign the informed consent and comply with study protocol.
• Must be ≥ 18 years of age (males and females).
• ≥ 1 lesion accessible for i.t. injection and biopsy(ies).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 minimum life expectancy ≥ 4 months.
• Adequate baseline organ function as defined by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/mm3)
• Platelet count ≥ 100 x 109/L (100,000/mm3)
• Hemoglobin ≥ 9.0 g/dL (5.59 mmol/L)
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance of ≥ 40 mL/minute (measured or calculated using the Cockroft-Gault formula)
• Aspartate aminotransferase (AST) ≤ 3 x ULN, alanine aminotransferase (ALT) ≤ 3 x ULN; AST/ALT \< 5 ULN if liver involvement
• ≤ 1.5 x ULN, except in subjects with Gilbert's syndrome who must have a total bilirubin ≤ 3 mg/dL
• Women of child bearing potential (WOCBP) and men with WOCBP partners must agree to use effective contraception methods as defined in the clinical study protocol.
• For any subjects who received prior approved/investigational i.t. anti-cancer treatments, the study's Medical Monitor must be consulted before enrollment.
• Histologically confirmed advanced, metastatic, or progressive MSS CRC based on either an analysis of tissue from a prior biopsy or based on tissue from a new biopsy. Subject's microsatellite/MMR status should be known.
• Received two prior lines of therapy for advanced or metastatic CRC including fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens. Subjects who relapse within 6 months of adjuvant chemotherapy composed of oxaliplatin and a fluoropyrimidine will have their adjuvant therapy count as one prior regimen.

You may not qualify if:

• Subject must have completed or completely discontinued any previous cancer-related treatments before enrollment with necessary windows and wash out periods as defined in the clinical study protocol.
• History of interstitial lung disease, pneumonitis, known or suspected autoimmune diseases (unless for specific diseases as defined in protocol) or human immunodeficiency virus (HIV) infection.
• Prior therapy with TLR9 agonist, excluding topical agents.
• Known hypersensitivity to any study drug component.
• Treatment with botanical preparations (e.g. herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment.
• Known or suspected autoimmune diseases. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to be enrolled.
• Subject with a requirement of systemic steroids \> 10 mg/day of prednisone (or equivalent) for the 2 weeks preceding start of study treatment.
• Subject with another primary malignancy that has not been in remission for at least 3 years except for non-melanoma skin cancer, curatively treated localized prostate cancer with non-detectable prostate specific antigen, cervical carcinoma in situ on biopsy, or thyroid cancer (except anaplastic).
• Active systemic infections requiring antibiotics.
• Active Hepatitis A, B or C infections.
• Known diagnosis of human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
• Women who are breast feeding or pregnant.
• Prior anaphylactic or other severe infusion reaction associated with human antibody administration that cannot be managed by standard supportive measurements.
• Presence of known central nervous system (CNS), meningeal, or epidural metastatic disease.However, subjects with known brain metastases are allowed if brain metastases are stable for≥ 4 weeks before the first dose of study treatment. Stable is defined as neurological symptoms not present or resolved at baseline, no radiological evidence of progression, and steroid requirement of prednisone ≤ 10 mg/day or equivalent.
• Subject with unstable and impaired cardiac function or clinically significant cardiac disease per Investigator's clinical judgment.

Sponsors & Collaborators

• Idera Pharmaceuticals, Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Banner University Medical Center Tucson Campus

Tucson, Arizona, 85719, United States

Location

University of Southern California/ Hoag Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

tilsotolimod; Nivolumab; Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Idera Medical Director

  Idera Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: March 6, 2019
• Study Start: October 29, 2019
• Primary Completion: March 1, 2022
• Study Completion: April 1, 2022
• Last Updated: February 17, 2022

Record last verified: 2022-02

Locations

US (3)