Cohort 1: IO Naive Relapsed/Metastatic Squamous Cell Carcinoma of the Head and Neck MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Tilsotolimod
Product Code: IMO-2125
Pharmaceutical Form: Solution for injection
INN or Proposed INN: tilsotolimod
CAS Numb
Sponsors
Idera Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject must be willing and able to sign the informed consent and comply with study protocol. 2. Must be = 18 years of age (males and females). 3. =1 lesion accessible for intratumoral 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: a) Absolute neutrophil count (ANC) = 1.5 x 109/L (1500/mm3) b) Platelet count = 100 x 109/L (100,000/mm3) c) Hemoglobin = 9.0 g/dL (5.59 mmol/L) d) Serum creatinine = 1.5 x upper limit of normal (ULN) or calculated creatinine clearance of = 40 mL/minute [= Grade 1] (measured or calculated using the Cockroft-Gault formula). e) Aspartate aminotransferase (AST) = 3 x ULN, alanine aminotransferase (ALT) = 3 x ULN; AST/ALT =65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: 1. Subject must have completed or completely discontinued any previous cancer-related treatments before enrollment. Any concurrent chemotherapy, radiotherapy, immunotherapy, or biologic or hormonal therapy for cancer excludes the subject (concurrent use of hormones for noncancer-related conditions [eg, insulin for diabetes and hormone replacement therapy] is acceptable). The following intervals between the end of the prior treatment and first dose of study drug must be observed: a) Port-a-cath placement: no waiting is required. b) Ongoing therapy at a stable dose greater than 2 months duration prior to enrollment and directed to maintaining a stable hormonal milieu (eg, Lupron in prostate cancer subjects) is allowed. c) Major surgery (as assessed by Investigator) or radiotherapy: = 4 weeks (subjects who receive palliative radiation for non-target tumor lesions need not be subjected to this washout period and can be enrolled immediately). d) Chemotherapy within 21 days or 5 half-lives (whichever is shorter) from enrollment. e) Immunotherapy and/or investigational anticancer therapy with agents including monoclonal antibodies = 4 weeks (with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent). 2. History of interstitial lung disease or pneumonitis. 3. Prior therapy with TLR9 agonist, excluding topical agents. 4. Known hypersensitivity to any study drug component. 5. Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to study treatment. 6. Prior immune-mediated AE of intensity Grade = 3. 7. Known or suspected autoimmune diseases. Subjects with type I diabetes mellitus or 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 enroll. Subject with a requirement of systemic steroids should be receiving = 10 mg/day of prednisone (or equivalent) for the 2 weeks preceding start of study treatment. 8. 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). 9. Active systemic infections requiring antibiotics. 10. Known active hepatitis A, B, or C infections. 11. Known diagnosis of human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS). 12. Women who are breast feeding or pregnant. 13. Prior anaphylactic or other severe infusion reaction associated with human antibody administration that cannot be managed by standard supportive measurements. 14. 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 befor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 objectives: Demonstrate the efficacy (measured by ORR based on RECIST v1.1) of intratumoral tilsotolimod in combination with nivolumab and ipilimumab. Part 2 objectives: If conducted, the overall objective of Part 2 is to assess the combination treatment effect. Part 2 endpoints will be determined after the decision is made to initiate Part 2 of the given cohort and will be added by protocol amendment. ; Secondary Objective: • Safety and tolerability of the combination of tilsotolimod with nivolumab and ipilimumab • Evaluate plasma concentrations of tilsotolimod, nivolumab, and ipilimumab using sparse blood sampling • Immunogenicity of tilsotolimod in combination with nivolumab and ipilimumab ; Primary end point(s): Part 1 Endpoints: Efficacy Endpoint: 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. ;Timepoint(s) of evaluation of this end point: 4 weeks after the initial documentation of response. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Endpoints: Treatment-emergent AEs (TEAEs), serious AEs (SAEs), laboratory evaluations, vital signs, and physical examinations. Pharmacokinetic Endpoint: Plasma concentrations will be determined for tilsotolimod, nivolumab, and ipilimumab. Immunogenicity Endpoint: Antidrug antibody (ADA) levels of tilsotolimod when combined with nivolumab and ipilimumab. Exploratory Endpoints: Tumor- and blood-based biomarkers in archival or baseline and paired biopsy samples will be evaluated for tumor genetics, characterization of immune infiltrates, and gene expression. ; Timepoint(s) of evaluation of this end point: Safety Endpoints: ongoing after tests are performed Pharmacokinetic Endpoint: after D-7, C1:D1 and C3:D1 Immunogenicity Endpoint: after D-7, C1:D1, C2:D1, C4:D1 and C7:D1 Exploratory Endpoints: at screening and after D-7, C1:D1, C2:D1, C3:D1, C4:D1, C5:D1, C6:D1 and C7:D1 | — |
Countries
Spain, United States
Contacts
Public ContactJennessa Martin
Idera Pharmaceuticals, Inc.
Outcome results
None listed