Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Skin Neoplasms

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 Diseases

Neuroendocrine Tumor

Neuroepithelioma

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Vitamins

Leucovorin

Levoleucovorin

Immunomodulating Agents

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Folinic Acid

IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous

Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.

IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod

Tilsotolimod with Ipilimumab

Idera Medical Director

A Phase 3 comparison of ipilimumab with and without IMO-2125 in advanced melanoma

A Phase 3 global, multi-center, open-label comparison of ipilimumab with and without intratumoral IMO-2125 in subjects with advanced melanoma who had confirmed disease progression while on anti-PD-1

A Study of Tilsotolimod in Combo With Ipilimumab vs Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma

A Randomized Phase 3 Comparison of IMO-2125 With Ipilimumab Versus Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma (ILLUMINATE-301)

The ORR for evaluable participants 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.

The calculation is derived from measuring the diameter (mm) of the target lesion at baseline and comparing target lesion diameter (mm) at intervals during treatment and/or post-treatment. Based on the percent of tumor decrease or increase, the appropriate category is assigned.

Efficacy measured by overall survival (OS) was defined as the number of participants alive compared to the number of participants that died by treatment group.

Bristol-Myers Squibb

Idera Pharmaceuticals, Inc.

Definitions aligned with FDA and ICH requirements.

The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as:

Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death

ipilimumab 3 mg/kg intravenous

ipilimumab: Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.

Arm A: Ipilimumab

IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous

Tilsotolimod with ipilimumab: IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod.

Arm B: IMO-2125 (Tilsotolimod) Plus Ipilimumab

ipilimumab 3 mg/kg intravenous

Ipilimumab: Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.

IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous

Tilsotolimod with Ipilimumab: IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod

Arm B: IMO-2125 Plus Ipilimumab

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

Netherlands

Sweden

United States

Czechia

Italy

United Kingdom

Australia

France

Germany

Spain

Region of Enrollment

Baseline Melanoma Characteristics

Measure Description: 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 Staging

Baseline Elevated LDH (lactate dehydrogenase)

The Eastern Cooperative Oncology Group (ECOG) Performance Status Scale describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). Scale grades are from 0 (fully active) best to 5 (dead) worst and are determined by physician assessment of the patient.

Grade:

0 - Fully active

1. - Restricted in physically strenuous activity
2. - Ambulatory, but unable to work
3. - Limited selfcare, confined to bed/chair \> 50% of waking hours
4. - Completely disabled, confined to bed/chair, no selfcare
5. - Dead

ECOG Performance Status

PD-1 Inhibitor

BRAK Inhibitor

MEK Inhibitor

Other

Other Immunotherapy

Cytokine

Chemotherapy

CTLA-4 Inhibitor

Oncolytic Virus

Other Targeted Therapy

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

Prior Systemic Anti-cancer Treatment

Unresectable/Metastatic Disease

Adjuvant

Neoadjuvant

Prior Systemic Anti-cancer Treatment Setting

Complete Response

Partial Response

Stable Disease

Progressive Disease

Unknown

Best Response from Last Prior Systemic Anti-cancer Treatment

Duration of Prior Anti-PD-1 Therapy

BRAF Mutation Status and Prior Targeted Therapy

Head of Clinical Operations

The ORR was defined as a percentage of subjects meeting criteria of CR and PR to calculate the p-value.

All percentages were based on the number of participants in the Intent-to-Treat (ITT) analysis set within each group. Participants with no disease assessment in the study were included in the Not Evaluable category under Best Overall Response.

Summary of Independent Reviewer-Assessed Objective Response Rate (ORR) by RECIST v1.1

All percentages were based on the number of participants in the Intent-to-Treat (ITT) analysis set within each group.

Summary of Overall Survival

Overall Study

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Death

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Pharmaceutical Solutions

Pembrolizumab

Participants receive 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment.

Participants receive 200 mg of pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus placebo by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment.

Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

Administered as an IV infusion every 6 weeks (Q6W)

Normal saline solution administered as an IV infusion Q6W

Placebo

Medical Director

The purpose of this study is to determine the efficacy of pembrolizumab given in combination with either ipilimumab or placebo as first-line treatment in participants with metastatic non-small cell lung cancer (NSCLC). The primary hypothesis of this study is that overall survival (OS) and/or progression-free survival (PFS) is prolonged in participants who receive pembrolizumab and ipilimumab compared to those who receive pembrolizumab and placebo.

With Amendment 6 (effective date: 11-Dec-2020), active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded. Participants will discontinue ipilimumab and placebo and participants who remain on treatment will receive open-label pembrolizumab only.

Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (MK-3475-598/KEYNOTE-598)

A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo in Previously Untreated, Stage IV, Metastatic Non-small Cell Lung Cancer Subjects Whose Tumors Are PD-L1 Positive (TPS ≥ 50%) (KEYNOTE-598)

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pd

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact. The median survival (in months) and the associated 95% confidence intervals (CIs) were reported using Kaplan-Meier method was used. Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and predominant tumor history (squamous versus non-squamous) was used to estimate hazard ratio (HR) and 95% CIs for first course study treatment per protocol.

PFS was defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in sum of diameters of target lesions. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The median survival (in months) and associated 95% CIs were reported using Kaplan-Meier method. Cox regression model with Efron's method of tie handling with treatment as covariate stratified by ECOG performance status (0 vs. 1), geographic region of the enrolling site (East Asia vs. non-East Asia), and predominant tumor history (squamous vs. non-squamous) was used to estimate HR and 95% CIs for first course study treatment per protocol.

ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 by BICR. In this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per protocol the ORR was calculated using the Miettinen \& Nurminen method stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and predominant tumor history (squamous versus non-squamous) for the first course of study treatment.

For participants who demonstrated a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. Per protocol, the DOR for all participants who experienced a CR or PR was presented for the first course of study treatment.

TTD was defined as the time to the first onset of a 10-point or greater score deterioration from baseline in any one of the 3 symptoms (cough, pain in chest or shortness of breath), confirmed by a second adjacent 10-point or greater score deterioration from baseline. Cough was based on EORTC QLQ-LC13 question 1, pain in chest was based on EORTC QLQ-LC13 question 10, and shortness of breath was based on EORTC QLQ-C30 question 8. Per protocol, TTD was reported for first course study treatment.

An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Per protocol, the number of participants who experienced an AE were reported for the first course of study treatment and follow up.

An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Per protocol, the number of participants who discontinued study treatment due to an AE were reported for the first course of study treatment.

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. Per protocol, the change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score were presented for first course study treatment.

Merck Sharp & Dohme LLC

All-cause mortality was reported on all randomized participants (first and second course). Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. MedDRA preferred terms 'Neoplasm progression', 'Malignant neoplasm progression' and 'Disease progression' not related to the drug were excluded. Pembrolizumab + Ipilimumab (second course) was not reported since no participants were eligible for second course treatment.

Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (\~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to \~1 year).

Pembrolizumab+Ipilimumab (First Course)

Participants received 200 mg of pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus placebo by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only.

Pembrolizumab+Placebo (First Course)

Pembrolizumab + Placebo (Second Course)

Pembrolizumab + Ipilimumab

Participants received 200 mg of pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus placebo by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (\~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to \~1 year).

Pembrolizumab + Placebo

Male

Female

Undifferentiated

Sex/Gender, Customized

0 = Fully active; no performance restrictions

1 = Strenuous physical activity restricted; fully ambulatory & able to carry out light work

Eastern Cooperative Oncology Group (ECOG) performance status

Squamous

Non squamous

Tumor histology

East Asia

Non-East Asia

Geographic region

Senior Vice President, Global Clinical Development

Overall Survival (OS)

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)

Objective Response Rate (ORR) Per RECIST 1.1 Based on BICR

All randomized participants with confirmed complete response or partial response

Duration of Response (DOR) Per RECIST 1.1 Based on BICR

All participants randomized who received at least one dose of study treatment and had at least one EORTC QLQ-LC13 and EORTC QLQ-C30 available.

Time to True Deterioration (TTD) in Cough, Pain in Chest, and Shortness of Breath

All randomized participants who received at least one dose of study treatment.

Number of Participants Who Experienced an Adverse Event (AE)

Number of Participants Who Discontinued Study Treatment Due to an AE

All randomized participants who received at least one dose of study treatment and had at least one EORTC QLQ-C30 assessment available.

Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Scale Score to Week 18

Cholangiocarcinoma

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulins, Intravenous

Immunologic Factors

After 4 cycles of PD-L1 antibody combined with CTLA-4 antibody treatment, PD-L1 monotherapy was maintained until the disease progressed or intolerable toxicity and adverse reactions or the medication was used for two years.

After 4 cycles of PD-L1 monoclonal antibody combined with CTLA-4 monoclonal antibody treatment, PD-L1 monotherapy was maintained until the disease progressed or intolerable toxicity and adverse reactions or the medication was used for two years.

PD-L1 antibody combined with CTLA-4 antibody

shi Guo-ming, MD

Shi Guo-ming, MD

Fan Jia, MD&PhD

Huang xiaoyong

Fan Jia, MD & PhD

The study aims to evaluate the efficacy and safety of PD-L1 antibody combined with the CTLA-4 antibody in patients with advanced ICC who progressed after standard treatment.

The prognosis of unresectable and metastatic intrahepatic biliary tract cancer (ICC) is extremely poor. The median overall survival of first-line gemcitabine and cisplatin for advanced biliary tumors (including ICC) is only 11.7 months. Currently, there is no standard second-line or third-line treatment for advanced ICC, and there is an urgent need to develop new treatment methods to improve patient survival. Chronic inflammation caused by viral infections and bile duct stones is the most common potential risk factor for ICC. The abnormal immune system plays a key role in the occurrence and development of ICC. The immune checkpoint molecules PD-L1 and CTLA-4 are overexpressed in ICC, and they are obviously heterogeneous, so immunotherapy has potential value. Immune checkpoint inhibitors against PD-1/PD-L1 show a good objective remission rate in advanced biliary tumors (including ICC). CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors show significant clinical enhancement Role, CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors have been clinically studied in a number of solid tumors. In this phase II clinical study, we will evaluate the efficacy and safety of PD-L1 monoclonal antibody combined with CTLA-4 monoclonal antibody in patients with advanced ICC who progressed after standard treatment.

PD-L1 Antibody Combined With CTLA-4 Antibody for Patients With Advanced Intrahepatic Cholangiocarcinoma Who Progressed After Standard Treatment

PD-L1 Antibody Combined With CTLA-4 Antibody for Patients With Advanced Intrahepatic Cholangiocarcinoma Who Progressed After Standard Treatment: a Single-arm, Phase II Clinical Study

the objective response rate (ORR) of advanced ICC patients who progressed after standard treatment with PD-L1 antibody SHR-1316 combined with CTLA-4 antibody IBI310

From the beginning date of combined therapy to the date of death

From the beginning date of combined therapy to disease progresion or death, whichever occurs first

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Tilsotolimod in Combo With Ipilimumab vs Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma	NCT03445533	Metastatic Mela...	Ipilimumab Tilsotolimod wi...	18 Years -	Idera Pharmaceuticals, Inc.
Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (MK-3475-598/KEYNOTE-598)	NCT03302234	Carcinoma, Non-...	Pembrolizumab Ipilimumab Placebo	18 Years -	Merck Sharp & Dohme LLC
PD-L1 Antibody Combined With CTLA-4 Antibody for Patients With Advanced Intrahepatic Cholangiocarcinoma Who Progressed After Standard Treatment	NCT04634058	Cholangiocarcin... PD-L1 CTLA4	PD-L1 antibody ...	18 Years -	Shanghai Zhongshan Hospital
PARP-inhibition and CTLA-4 Blockade in BRCA-deficient Ovarian Cancer	NCT02571725	Ovarian Cancer Fallopian Tube ... Peritoneal Neop...	Olaparib Tremelimumab	18 Years -	New Mexico Cancer Care Alliance
PARP-inhibition and CTLA-4 Blockade in BRCA-deficient Ovarian Cancer	NCT02571725	Ovarian Cancer Fallopian Tube ... Peritoneal Neop...	Olaparib Tremelimumab	18 Years -	New Mexico Cancer Care Alliance
GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR-T Cells Against Cancers	NCT03198052	Lung Cancer Cancer Immunotherapy CAR-T Cell	CAR-T cells tar...	18 Years - 75 Years	Second Affiliated Hospital of Guangzhou Medical University

Spots Global Cancer Trial Database for ctla4

Every month we try and update this database with for ctla4 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ctla4

Every month we try and update this database with for ctla4 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ctla4 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.