Clinical Trials /

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

NCT03865082

Description:

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

Related Conditions:
  • Colorectal Carcinoma
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Tilsotolimod in Combination With Nivolumab and Ipilimumab for the Treatment of Solid Tumors (ILLUMINATE-206)
  • Official Title: Study of Tilsotolimod in Combination With Nivolumab and Ipilimumab for the Treatment of Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 2125-MST-206
  • NCT ID: NCT03865082

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
TilsotolimodIMO-2125IO Naive Subjects RM SCCHN
NivolumabOPDIVOIO Naive Subjects RM SCCHN
IpilimumabYervoyIO Naive Subjects RM SCCHN
IpilimumabYervoyIO Naive Subjects MSS CRC

Purpose

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

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
    

Trial Arms

NameTypeDescriptionInterventions
IO Naive Subjects RM SCCHNExperimentalTilsotolimod by intratumoral injection plus Nivolumab and Ipilimumab intravenous
  • Tilsotolimod
  • Nivolumab
  • Ipilimumab
IO Naive Subjects MSS CRCExperimentalTilsotolimod by intratumoral injection plus Nivolumab and Ipilimumab intravenous
  • Tilsotolimod
  • Nivolumab
  • Ipilimumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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).
Safety Issue:
Description:Efficacy measure by overall response rate (ORR)

Secondary Outcome Measures

Measure:Safety and tolerability of the combination of tilsotolimod with nivolumab and ipilimumab
Time Frame:At every study visit (up to 48 months)
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description:Plasma concentrations will be determined for tilsotolimod, nivolumab, and ipilimumab
Measure: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
Safety Issue:
Description:Anti-drug anitbody measures of tilsotolimod when combined with nivolumab and ipilimumab

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Idera Pharmaceuticals, Inc.

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