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

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ClinicalTrials.gov Identifier: NCT03865082
Recruitment Status : Not yet recruiting
First Posted : March 6, 2019
Last Update Posted : March 6, 2019
Sponsor:
Information provided by (Responsible Party):
Idera Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: Tilsotolimod Drug: Nivolumab Drug: Ipilimumab Phase 2

Detailed Description:
This is a Phase 2, open-label, global, multi-center, multicohort study of intratumoral tilsotolimod in combination with nivolumab and ipilimumab for the treatment of specific solid tumors

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 77 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study of Tilsotolimod in Combination With Nivolumab and Ipilimumab for the Treatment of Solid Tumors
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IO Naive Subjects RM SCCHN
Tilsotolimod by intratumoral injection plus Nivolumab and Ipilimumab intravenous
Drug: Tilsotolimod
9 doses of Tilsotolimod Intratumoral injection administered as a dose of 8mg at Day -7 (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.
Other Name: IMO-2125

Drug: Nivolumab
Nivolumab 3 mg/kg intravenous q2w over 30 minutes infusion. Nivolumab administration may continue for up to 2 years or until disease progression, whichever is earlier.
Other Name: OPDIVO

Drug: Ipilimumab
Ipilimumab 1 mg/kg intravenous q6w over 30 minutes. Ipilimumab administration may continue for up to 2 years or until disease progression, whichever is earlier
Other Name: Yervoy

Experimental: IO Naive Subjects MSS CRC
Tilsotolimod by intratumoral injection plus Nivolumab and Ipilimumab intravenous
Drug: Tilsotolimod
9 doses of Tilsotolimod Intratumoral injection administered as a dose of 8mg at Day -7 (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.
Other Name: IMO-2125

Drug: Nivolumab
Nivolumab 3 mg/kg intravenous q2w over 30 minutes infusion. Nivolumab administration may continue for up to 2 years or until disease progression, whichever is earlier.
Other Name: OPDIVO

Drug: Ipilimumab
Ipilimumab 1 mg/kg intravenous q8w over 30 minutes. Ipilimumab administration may continue for up to 2 years or until disease progression, whichever is earlier
Other Name: Yervoy




Primary Outcome Measures :
  1. Demonstrate the efficacy of intratumoral tilsotolimod in combination with ipilimumab and nivolumab for each cohort [ Time Frame: 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). ]
    Efficacy measure by overall response rate (ORR)


Secondary Outcome Measures :
  1. Safety and tolerability of the combination of tilsotolimod with nivolumab and ipilimumab [ Time Frame: At every study visit (up to 48 months) ]
    Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms(ECGs), safety and laboratory parameters as assessed by CTCAE v4.03

  2. Evaluate plasma concentrations of tilsotolimod, nivolumab, and ipilimumab using sparse blood sampling [ Time Frame: Screening, Day -7, Cycle 1 Day 1 and Cycle 3 Day 1 (up to 17 weeks). Each cycle is 28 days ]
    Plasma concentrations will be determined for tilsotolimod, nivolumab, and ipilimumab

  3. Immunogenicity of tilsotolimod in combination with nivolumab and ipilimumab [ Time Frame: Screening, Day -7, Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1 and Cycle 7 Day 1, (up to 32 weeks). Each cycle is 28 days ]
    Anti-drug anitbody measures of tilsotolimod when combined with nivolumab and ipilimumab



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  1. Subject ≥ 18 years of age (males and females)
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 minimum life expectancy ≥ 4 months, adequate organ functions, and ≥1 lesion accessible for intratumoral injection and biopsy(ies).
  3. Women of child bearing potential (WOCBP) and men with WOCBP partners must agree to use effective contraception methods as defined I n the clinical study protocol.

Inclusion Criteria (RM SCCHN IO Naïve):

  1. Histologically and/or cytologically confirmed recurrent or metastatic, PD(L)1 negative or positive SCCHN (oral cavity, oropharynx, larynx, or hypopharynx) that is not amenable to curative therapy (by surgery or radiation with or without chemotherapy).
  2. At least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, minimum 10 mm except lymph nodes (minimum short axis 15 mm). Target lesions may be in a previously irradiated field if there is documented (radiographic) disease progression in that site after the completion of radiation therapy.

Inclusion Criteria ( MSS CRC IO Naïve)

  1. 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.
  2. Received at least two prior regimens 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.
  3. Documentation of radiologic progression by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 during or after previous chemotherapy.

Main Exclusion Criteria:

  1. 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.
  2. 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.
  3. Prior therapy with TLR9 agonist, excluding topical agents.
  4. Known hypersensitivity to any study drug component.
  5. Prior immune-mediated AE of intensity Grade ≥ 3.
  6. 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).
  7. Active systemic infections requiring antibiotics, active Hepatitis A, B or C infections.
  8. Women who are breast feeding or pregnant.
  9. Prior anaphylactic or other severe infusion reaction associated with human antibody administration that cannot be managed by standard supportive measurements.
  10. Presence of unstable central nervous system disease involvement
  11. Subject with unstable and impaired cardiac function or clinically significant cardiac disease per Investigator's clinical judgment.
  12. Has received live attenuated vaccine 30 days before first study dose.

Exclusion Criteria ((RM SCCHN IO Naïve):

  1. Subject with squamous cell carcinoma of any other primary anatomic location in the head and neck (eg, paranasal cavity), subjects with squamous cell carcinoma of unknown primary, and subject with nonsquamous histologies of head and neck tumors.
  2. Subject who received prior systemic therapy for SCCHN in the recurrent or metastatic setting (exception: subject with persistent disease after treatment in locally advanced setting).
  3. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor in approved or experimental setting.
  4. The only lesion available for injection is in close proximity to or invading a major blood vessel (such as the carotid artery).

Exclusion Criteria (MSS CRC IO Naïve):

  1. Prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death ligand-1 (PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor in an approved or experimental setting.
  2. Subjects with BRAF V600E mutations.
  3. Subjects with a history of immune-mediated colitis.

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Responsible Party: Idera Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03865082     History of Changes
Other Study ID Numbers: 2125-MST-206
First Posted: March 6, 2019    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents