Clinical Trials /

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



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

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:



Phase 2

Trial Eligibility



  • 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


  • Solid Tumor


TilsotolimodIMO-2125IO Naive Subjects MSS CRC
NivolumabOPDIVOIO Naive Subjects MSS CRC
IpilimumabYervoyIO Naive Subjects MSS CRC


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

Detailed Description

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

Trial Arms

IO Naive Subjects MSS CRCExperimental8mg 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
  • Tilsotolimod
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Main Inclusion Criteria:

          1. Subject must be willing and able to sign the informed consent and comply with study

          2. Must be ≥ 18 years of age (males and females).

          3. ≥ 1 lesion accessible for i.t. injection and biopsy(ies).

          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 minimum life
             expectancy ≥ 4 months.

          5. Adequate baseline organ function as defined by:

               1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/mm3)

               2. Platelet count ≥ 100 x 109/L (100,000/mm3)

               3. Hemoglobin ≥ 9.0 g/dL (5.59 mmol/L)

               4. 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

               5. Aspartate aminotransferase (AST) ≤ 3 x ULN, alanine aminotransferase (ALT) ≤ 3 x
                  ULN; AST/ALT < 5 ULN if liver involvement

               6. ≤ 1.5 x ULN, except in subjects with Gilbert's syndrome who must have a total
                  bilirubin ≤ 3 mg/dL

          6. 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.

          7. For any subjects who received prior approved/investigational i.t. anti-cancer
             treatments, the study's Medical Monitor must be consulted before enrollment.

        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 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.

          3. Documentation of radiologic progression by Response Evaluation Criteria in Solid
             Tumors (RECIST) v1.1 during or after previous chemotherapy. Subjects documented
             clinical progression may be eligible and must be discussed with the medical monitor to
             determine eligibility.

        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. 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.

          6. 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.

          7. 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).

          8. Active systemic infections requiring antibiotics.

          9. Active Hepatitis A, B or C infections.

         10. 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.

         11. Women who are breast feeding or pregnant.

         12. Prior anaphylactic or other severe infusion reaction associated with human antibody
             administration that cannot be managed by standard supportive measurements.

         13. 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.

         14. Subject with unstable and impaired cardiac function or clinically significant cardiac
             disease per Investigator's clinical judgment.

         15. Has received live attenuated vaccine 30 days before first study dose. Any live
             attenuated vaccine [e.g., varicella, zoster, yellow fever, rotavirus, oral polio and
             measles, mumps, rubella (MMR)] during treatment and until 100 days post last dose will
             be prohibited.

        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.

          4. Subjects who received three or more lines of therapy for advanced or metastatic CRC
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 objective response rate

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 or higher.


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Idera Pharmaceuticals, Inc.

Last Updated

July 21, 2021