Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Combination between nivolumab IV Q3W and dual intratumoral injections of Ipilimumab and Tilsotolimod Q3W

Combination between nivolumab IV Q3W and dual intratumoral injections of Ipilimumab and Tilsotolimod QW

Tilsotolimod

Open label, phase Ib study of intratumoral tilsotolimod in combination with intratumoral ipilimumab and intravenous nivolumab.

The trial will be divided into two parts:

PART A:

the first part will assess the safety of two regimen and will recruit patients with all types of injectable solid malignancies

PART B:

the second part will include 3 expansion cohorts of 15 patients:

* B1: anti-PD-1 refractory advanced NSCLC cohort
* B2: anti-PD-1 refractory advanced melanoma cohort
* B3: immunotherapy naïve microsatellite stable colorectal cancer (MSS CRC) cohort

Open label, phase Ib study of intratumoral tilsotolimod in combination with intratumoral ipilimumab and intravenous nivolumab.

Intratumoral Tilsotolimod, a TLR-9 Agonist, Together With Intratumoral Ipilimumab and Intravenous Nivolumab in Patients With Advanced Cancers

A Phase I Trial Assessing the Safety and Efficacy of an Anti-tumor Immunity Priming Strategy Combining Intratumoral Tilsotolimod, a TLR-9 Agonist, Together With Intratumoral Ipilimumab and Intravenous Nivolumab in Patients With Advanced Cancers

Gustave Roussy, Cancer Campus, Grand Paris

Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Micronutrients

Vitamins

Leucovorin

Levoleucovorin

Folinic Acid

Intradermal, single injection of 1 ml (8 mg) Tilsotolimod (IMO-2125) at the primary melanoma excision site, one week prior to sentinel node biopsy (SNB).

Intradermal, single injection of 1 ml plain saline (0.9% sodium chloride) at the primary melanoma excision site, one week prior to sentinel node biopsy (SNB).

Saline (0.9% sodium chloride)

Jessica CL Notohardjo, MD

Tanja de Gruijl

Alfons JM van den Eertwegh

Currently, there is no widely used adjuvant treatment available to improve survival after surgical excision of a primary melanoma. In a previous study, loco-regional and systemic immune stimulations, as well as favourable clinical outcomes in terms of sentinel lymph node (SLN) tumor status and recurrence-free survival (RFS) in patients with clinical stage I-II melanoma who received a low dose of toll-like receptor 9 (TLR-9) CPG7909 (CpG-B ODN) intradermally at the excision site of the primary tumor prior to SLN biopsy (SNB) were described. In this phase II trial the investigators had investigated the clinical activity of a next-generation CpG-ODN, IMO-2125, and it's ability to induce loco-regional and systemic immune stimulation in pT3-4 cN0M0 melanoma patients who are scheduled to undergo a combined re-excision and SNB is

A Randomized Controlled Phase II Multicenter Clinical Trial

Persons that are masked/ blinded for which medication the patient receives: participant, treating physician/ team (including the person giving the intradermal injection) and peron who collects the data.

A Randomized Controlled Phase II Trial With Intradermal IMO-2125 in Pathological Tumor Stage (p) T3-4 cN0M0 Melanoma

A Randomized Controlled Phase II Clinical Trial With Intradermal IMO-2125 (Tilsotolimod) in pT3-4 cN0M0 Melanoma

The rate of tumor positive sentinal lymph node (SLN)

Frequency and activation state of lymph node resident (LNR) conventional dendritic cells (DC) and melanoma antigen-specific T cell responses in the SLN and peripheral blood.

The length of time from intradermal injection of Tilsotolimod (IMO-2125) to first documentation of recurrence.

The length of time from intradermal injection of Tilsotolimod (IMO-2125) to death from any cause.

Idera Pharmaceuticals, Inc.

A.J.M. van den Eertwegh

Principal Investigator

Pembrolizumab

IMO-2125 intratumoral injection plus ipilimumab

Drug: IMO-2125 Intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 17, 23, and 29.

IMO-2125

4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 2, 5, 8, and 11.

Idera Medical Director

The goal of the Phase 1 study was to find the recommended Phase 2 dose of the study drug IMO-2125 (tilsotolimod) that can be given in combination with ipilimumab (ipi) or pembrolizumab (pembro) to participants with metastatic melanoma and assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity when administered in combination with ipilimumab or pembrolizumab.

The open-label single-arm Phase 2 study was designed to assess the recommended dose for safety, tolerability, pharmacokinetics (PK), immunogenicity, and efficacy of 8 mg IMO-2125 (tilsotolimod) when administered in combination with ipilimumab.

A Phase 2 Study to Assess the Safety and Efficacy of IMO-2125 With 8 mg Ipilimumab in Patients With Metastatic Melanoma

A Phase 1/2 Study to Assess the Safety and Efficacy of Intratumoral IMO-2125 in Combination With Ipilimumab or Pembrolizumab in Patients With Metastatic Melanoma (ILLUMINATE-204)

The following combined analysis populations were used for outcome measures (efficacy analysis N=53):

* The Phase 2, 8 mg Tilso/Ipi efficacy evaluable population (N=44)
* The Phase 1, 8 mg Tilso/Ipi evaluable population (N=9)

The ORR for 49 evaluable (4 non-evaluable) participants who received the recommended Phase 2 dose (RP2D) of 8 mg Tilso/Ipi was calculated using the participant's best overall response (BOR).

Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target lesions as assessed by MRI, CT or X-ray: Complete Response (CR) - disappearance of all target lesions; Partial Response (PR) - \>=30% decrease from baseline of the sum of diameters of all target lesions; Stable Disease (SD) - does not qualify for CR, PR or Progression; Progressive Disease (PD) - 20% increase in the sum of diameters of target lesions.

Overall Response = CR or PR

The following combined analysis populations were used for outcome measures (efficacy analysis N=53):

* The Phase 2, 8 mg Tilso/Ipi efficacy evaluable population N=40 (44 with 4 non-evaluable)
* The Phase 1, 8 mg Tilso/Ipi evaluable population (N=9)

Progression-free survival was defined as the number of months from the initiation of treatment to confirmed disease progression using RECIST v1.1 or death from any cause.

The following combined analysis populations were used for outcome measures (efficacy analysis N=53):

* The Phase 2, 8 mg Tilso/Ipi efficacy evaluable population N=44 (40 with 4 non-evaluable)
* The Phase 1, 8 mg Tilso/Ipi evaluable population (N=9)

Overall survival was defined as the number of months from initiation of treatment to death from any cause.

The following combined analysis populations were used for outcome measures (efficacy analysis N=53):

* The Phase 2, 8 mg Tilso/Ipi efficacy evaluable population N=40 (44 with 4 non-evaluable)
* The Phase 1, 8 mg Tilso/Ipi evaluable population (N=9)

Overall survival was defined as the number of months from initiation of treatment to death from any cause.

Definitions aligned with FDA and ICH requirements.

Arm/Group includes 9 participants rolled over from Phase 1, 8 mg Tilso/Ipi.

IMO-2125 intratumoral injection plus ipilimumab

IMO-2125: Drug: IMO-2125 (8 mg as the RP2D) Intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 17, 23, and 29.

Ipilimumab: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 2, 5, 8, and 11.

Phase 2, 8 mg Tilso/Ipi

IMO-2125 intratumoral injection plus ipilimumab

IMO-2125: Drug: IMO-2125 (8 mg as the RP2D) Intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 17, 23, and 29.

Ipilimumab: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 2, 5, 8, and 11.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Body Mass Index

Baseline Melanoma Characteristics

Physician assessed and determined based on American Joint Committee on Cancer (AJCC) Staging System for Melanoma, Seventh Edition, which determines the stage (I-V) based on the TNM classification. T refers to tumor size, N refers to nearby lymph nodes and M represents metastasized (spread) to other parts of the body. This staging number is obtained as a sum of the TNM classification. The lower the number, the lower the cancer stage and the better the prognosis for the patient. The higher the stage, the worse the prognosis for the patient.

Baseline Melanoma Stage

Baseline Brain Metastases

Baseline Visceral Metastases

Baseline Elevated LDH

Baseline BRAF Mutation

Therapeutic Lymph Node Dissection

Radiation

Chemotherapy

Interferon

BRAF Inhibitor

MEK Inhibitor

CTLA-4 Inhibitor

PD-(L)1 Inhibitor

Other

Indicates multiple, known prior melanoma treatments. Participants may be counted in more than one category based on combination of prior melanoma treatments.

Prior Melanoma Treatment

Includes all participants who received at least 1 dose of study treatment.

The analysis populations, as defined in section 6 of the Statistical Analysis Plan, analyzed participants enrolled in the phase 2 study (N=44) and participants rolled in from the phase 1, 8 mg Tilso/Ipi population (N=9).

Head of Clinical Operations

Testing the best overall confirmed response rate against the historical control rate of 0.11 (extracted from the literature review).

Arm/Group includes 9 participants rolled over from Phase 1 8mg Tilso/Ipi

IMO-2125 (tilso) intratumoral injection plus ipilimumab (ipi)

IMO-2125 (tilso): Drug: IMO-2125 (tilso) (8 mg as the RP2D) Intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 17, 23, and 29.

Ipilimumab (ipi): 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 2, 5, 8, and 11.

Per the SAP, section 6, Analysis Populations used for efficacy, the analysis populations utilize both PIIEE (Primary Ipilimumab + IMO-2125 Efficacy Evaluable) who are ipilimumab-naive and SIIEE (Secondary Ipilumumab + IMO-2125 Efficacy Evaluable) who are not ipilumumab-naive that were treated at the RP2D, regardless of phase, and received at least one dose of each study drug.

Phase 2: Number of Participants With Objective Response Rate (ORR) Using RECIST v1.1

Phase 2: Progression-free Survival

Phase 2: Overall Survival - 6 Months

Phase 2: Overall Survival - 12 Months

IMO-2125 (tilso) intratumoral injection plus ipilimumab (ipi)

IMO-2125 (tilso): Drug: IMO-2125 (tilso) (8 mg as the RP2D) Intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 17, 23, and 29.

Ipilimumab (ipi): 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 2, 5, 8, and 11.

Overall Study

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

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.

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

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

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

Study of Tilsotolimod in Combination With Nivolumab and Ipilimumab for the Treatment of Solid Tumors

Efficacy measure by objective response rate

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.

Bristol-Myers Squibb

Symptoms and General Pathology

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Participants will be administered ABBV-368 and Tilsotolimod at various timepoints as described in the protocol.

Participants will be administered ABBV-368, Tilsotolimod and Nab-paclitaxel at various timepoints as described in the protocol.

Participants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol.

ABBV-368

Nab-paclitaxel

ABBV-181

ABBVIE INC.

The main objective of this study is to assess safety, tolerability, and pharmacokinetics (PK) of ABBV-368 plus tilsotolimod; ABBV-368 plus tilsotolimod and nab-paclitaxel; and ABBV-368 plus tilsotolimod, nab-paclitaxel, and ABBV-181 in participants with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-368 Plus Tilsotolimod and Other Therapy Combinations in Participants With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

A Phase 1b, Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-368 Plus Tilsotolimod and Other Therapy Combinations in Subjects With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.

Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.

Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.

Maximum Serum Concentration (Cmax) of ABBV-368

Time to Maximum Serum Concentration (Tmax) of ABBV-368

Area Under Serum Concentration-Time Curve of ABBV-368 From Time 0 to the Time of Last Measurable Concentration (AUCt)

Terminal-Phase Elimination Rate Constant (β) of ABBV-368

Maximum Observed Plasma Concentration (Cmax) of Tilsotolimod

Time to Maximum Plasma Concentration (Tmax) of Tilsotolimod

Area Under Plasma Concentration-Time Curve of Tilsotolimod From Time 0 to the Time of Last Measurable Concentration (AUCt)

Terminal-Phase Elimination Rate Constant (β) of Tilsotolimod

Terminal Half-Life (t1/2) of Tilsotolimod

Maximum Observed Serum Concentration (Cmax) of ABBV-181

Time to Maximum Serum Concentration (Tmax) of ABBV-181

Area Under Serum Concentration-Time Curve of ABBV-181 From Time 0 to the Time of Last Measurable Concentration (AUCt)

Terminal-Phase Elimination Rate Constant (β) of ABBV-181

ORR is measured as the percentage of participants with a complete response (CR) or partial response (PR) as a confirmed response.

CBR is measured as the percentage of participants with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD)

TTR is the time from date of first study drug exposure to the first instance of a complete response (CR) or partial response (PR) as a confirmed response, whichever occurs first.

PFS is the time from date of first study drug exposure to disease progression or death, whichever occurs first.

DOR is the time from the participant's initial response (CR or PR as a confirmed response) to disease progression or death, whichever occurs first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intratumoral Tilsotolimod, a TLR-9 Agonist, Together With Intratumoral Ipilimumab and Intravenous Nivolumab in Patients With Advanced Cancers	NCT04270864	Advanced Cancer	Ipilimumab Nivolumab Tilsotolimod	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris
A Randomized Controlled Phase II Trial With Intradermal IMO-2125 in Pathological Tumor Stage (p) T3-4 cN0M0 Melanoma	NCT04126876	Malignant Melan...	Tilsotolimod Saline (0.9% so...	18 Years -	Amsterdam UMC, location VUmc
A Phase 2 Study to Assess the Safety and Efficacy of IMO-2125 With 8 mg Ipilimumab in Patients With Metastatic Melanoma	NCT02644967	Metastatic Mela...	IMO-2125 Ipilimumab	18 Years -	Idera Pharmaceuticals, Inc.
Study of Tilsotolimod in Combination With Nivolumab and Ipilimumab for the Treatment of Solid Tumors (ILLUMINATE-206)	NCT03865082	Solid Tumor	Tilsotolimod Nivolumab Ipilimumab	18 Years -	Idera Pharmaceuticals, Inc.
A Phase 2 Study to Assess the Safety and Efficacy of IMO-2125 With 8 mg Ipilimumab in Patients With Metastatic Melanoma	NCT02644967	Metastatic Mela...	IMO-2125 Ipilimumab	18 Years -	Idera Pharmaceuticals, Inc.
A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-368 Plus Tilsotolimod and Other Therapy Combinations in Participants With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma	NCT04196283	Advanced Solid ...	ABBV-368 Tilsotolimod Nab-paclitaxel ABBV-181	18 Years -	AbbVie

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