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IMC-1121B

Phase 2

Cancer | Monoclonal antibody | Oncology |Eli Lilly and Company|Last Updated: Sep 13, 2019

Success Probability

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Market & Valuation

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Trial Design

UNCONTROLLED
Total Trials2
Total Enrollment93

FDA Designations

No designations recorded

Clinical trial landscape

IMC-1121B · 7 trials · 6 indications

Phase 2 4Phase 1 3
NCT01160744A Study of Pemetrexed and Carboplatin/Cisplatin or Gemcitabine and Carboplatin/Cisplatin With or Without IMC-1121B in Participants Previously Untreated With Recurrent or Advanced Non-Small Cell Lung Cancer (NSCLC)Carcinoma, Non-Small-Cell Lung
COMPLETED280 Analytics
NCT01017731Study of Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval ChangesCancer
COMPLETED68 Analytics
NCT00862784A Study of IMC-1121B (Ramucirumab) in Colorectal CancerColorectal Carcinoma
COMPLETED48 Analytics
NCT00533702A Study of IMC-1121B (Ramucirumab) With or Without Dacarbazine in Metastatic Malignant MelanomaMetastatic Malignant Melanoma
COMPLETED106 Analytics
PHASE2COMPLETED
A Study of Pemetrexed and Carboplatin/Cisplatin or Gemcitabine and Carboplatin/Cisplatin With or Without IMC-1121B in Participants Previously Untreated With Recurrent or Advanced Non-Small Cell Lung Cancer (NSCLC)
Carcinoma, Non-Small-Cell LungUnlock trial analytics
PHASE2COMPLETED
Study of Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes
CancerUnlock trial analytics
PHASE2COMPLETED
A Study of IMC-1121B (Ramucirumab) in Colorectal Cancer
Colorectal CarcinomaUnlock trial analytics
PHASE2COMPLETED
A Study of IMC-1121B (Ramucirumab) With or Without Dacarbazine in Metastatic Malignant Melanoma
Metastatic Malignant MelanomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Progression-Free Survival (PFS)
Randomization to PD or death (up to 24 months)

PFS was the time from randomization to the first objective progression as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1) or death from any cause, whichever occurred first. Progressive disease (PD) was defined as ≥20% increase in sum of diameter (SOD) of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 millimeters (mm); appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants alive and without disease progression were censored at the time of the last objective tumor assessment. Participants who did not progress and were lost to follow-up were censored at their last radiographic assessment. If no baseline or post baseline radiologic assessments were available, participants were censored at date of randomization.

Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants
Baseline, Cycle 3 (1 cycle=21 days)

All electrocardiogram (ECG) tests were performed in triplicate prior to ramucirumab treatment. QT is the interval between the Q and T waves and QTc is the QT corrected for heart rate using Fridericia's formula: QTc = QT/RR\^0.33 where RR is the interval between 2 R waves. Each participant's mean QT/QTc value was calculated for each ECG test during Cycle 3 and compared to his/her mean pretreatment QT/QTc value. The greatest change from baseline during Cycle 3 was reported. QTc prolongation is defined as a QTc exceeding 10 milliseconds (msec) with a lower 90% confidence interval (CI) exceeding 5 msec at any postdose time points per the International Conference on Harmonization (ICH) E14 guidelines for non-thorough QT studies (ICH 2005; ICH 2008). Least squares (LS) mean was calculated using a linear mixed model for repeated measures (MMRM) and adjusted for serum concentration.

Progression Free Survival (PFS)
Baseline up to 36 months

PFS was defined as the time from the first day of therapy to the first evidence of disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the longest diameter (LD) of the target lesions, taking as reference the smallest sum LD recorded since the treatment started in comparison with the measurement of the nadir or the appearance of 1 or more new lesions. In addition, unequivocal progression of existing non-target lesions was considered PD. New or existing pleural effusion/ascites required cytological confirmation for PD according to the protocol. Participants who did not progress and who were alive or did not have documented progression or missed ≥2 visits, or had no post baseline assessment were censored at the day of their last tumor assessment.

Number of Participants With Drug-Related Adverse Events
Baseline to study completion up to 48 weeks

Data presented are the number of participants who experienced adverse events (AE) of any grade, AE of Grade ≥3 based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), serious adverse events (SAE) and AE resulting in death that was considered to be related to IMC-1121B (ramucirumab). A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.

IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2
Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 3 to 5
Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose

Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.

IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2
Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle

AUC for Cycle 1 is AUC from time zero to infinity \[AUC(0-∞)\] and for Cycle 2 is AUC over a dosing interval (AUCτ).

IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohorts 1 and 2 During Cycles 3 to 5
Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose

Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.

IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2
Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohorts 1 and 2 During Cycles 3 to 5
Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose

Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.

IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2
Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 3 to 5
Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose

Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.

IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 1 and 2
Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 3 to 5
Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose

Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.

IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohort 3 During Cycles 1 and 2
Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle

AUC for Cycle 1 is AUC from time zero to infinity \[AUC(0-∞)\] and for Cycle 2 is AUC over a dosing interval (AUCτ).

IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohort 3 During Cycles 3 to 5
Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose

Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.

IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2
Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohort 3 During Cycles 3 to 5
Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose

Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.

IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 1 and 2
Day 1 and Day 22 of Cycles 1 and 2 of a 6-week cycle
IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 3 to 5
Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour post-dose

Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.

Number of participants with Adverse Events (AEs)
8 Weeks
Maximum Tolerated Dose
8 Weeks

Secondary Endpoints

Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months)
Overall Survival (OS)
Randomization to the date of death from any cause (up to 31.3 months)
Duration of Response (DOR)
Time of first response (CR or PR) until PD or death (up to 24 months)
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
IMC-1121B + Pemetrexed + Carboplatin (AUC 6) or CisplatinEXPERIMENTALIMC-1121B + Pemetrexed + Carboplatin \[Area Under the Concentration Time Curve 6 (AUC 6)\] or Cisplatin
Pemetrexed + Carboplatin (AUC 6) or CisplatinACTIVE_COMPARATORPemetrexed + Carboplatin (AUC 6) or Cisplatin
IMC-1121B + Gemcitabine + Carboplatin (AUC 5) or CisplatinEXPERIMENTALIMC-1121B + Gemcitabine + Carboplatin \[Area Under the Concentration Time Curve 5 (AUC 5)\] or Cisplatin
Gemcitabine + Carboplatin (AUC 5) or CisplatinACTIVE_COMPARATORGemcitabine + Carboplatin (AUC 5) or Cisplatin
IMC-1121BEXPERIMENTALActive-control participants (first 16 participants) will receive one dose of moxifloxacin orally 7 days before the first treatment with ramucirumab. All participants will undergo triplicate electrocardiogram (ECG) tests (consisting of three individual ECGs performed consecutively within a period of 4 minutes) and vital signs at various times over the trial period. For Cycle 1, all participants will also receive 2 infusions of diphenhydramine before ramucirumab therapy (the first infusion is 1 day before therapy and the second infusion is 15 minutes before therapy). For Cycles 2, 3, and 4, all participants will receive diphenhydramine 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, diphenhydramine infusions before ramucirumab therapy are at the investigator's discretion. Ramucirumab \[10 milligrams per kilogram (mg/kg)\] intravenously over 60 minutes, once every 3 weeks for minimum of 9 weeks without a break in between.
IMC-1121B (ramucirumab) + mFOLFOX-6EXPERIMENTALThis regimen will be repeated every 2 weeks until disease progression, unacceptable toxicity, or withdrawal.
IMC-1121B (ramucirumab)EXPERIMENTALIMC-1121B (ramucirumab)
IMC-1121B (ramucirumab) + dacarbazineACTIVE_COMPARATORIMC-1121B (ramucirumab) + dacarbazine

Interventions

NameTypeDescription
IMC-1121B (ramucirumab)BIOLOGICAL10 milligrams/kilogram (mg/kg) once every 3 weeks beginning Day 1, Cycle 1
PemetrexedDRUG500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle
Carboplatin (AUC 6)DRUGDay 1 of every 21-day cycle
CisplatinDRUG75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle
GemcitabineDRUG1000 mg/m² on Days 1 and 8 of every 21-day cycle
Carboplatin (AUC 5)DRUGDay 1 of every 21-day cycle
IMC-1121BBIOLOGICALIMC-1121B (Ramucirumab) 10 mg/kg intravenously (IV) over 60 minutes, once every 3 weeks for minimum of 9 weeks.
MoxifloxacinDRUGAdministered orally
DiphenhydramineDRUGAdministered IV
OxaliplatinDRUG85 milligrams/square meter (mg/m²) intravenous infusion over 2 hours on Day 1
Folinic acidDRUG400 mg/m² intravenous infusion over 2 hours on Day 1
5-FUDRUG400 mg/m² intravenous bolus injection over 2-4 minutes, immediately following folinic acid infusion
DacarbazineDRUG1000 milligrams/square meter (mg/m2) intravenously every 3 weeks in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
1121BBIOLOGICALCohort 2 8mg/kg I.V., once every other week for 4 weeks
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites53

Inclusion Criteria: * Confirmed NSCLC * Stage IV disease at the time of study entry * Measurable disease at the time of study entry * Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (except alopeci...

Countries:United StatesBelgiumCanadaGermanyPolandUnited KingdomSpainJapan
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Frequently asked questions about IMC-1121B

What is IMC-1121B used for?

IMC-1121B is an investigational monoclonal antibody being studied for the treatment of advanced solid tumors, metastatic malignant melanoma, colorectal carcinoma, and non-small-cell lung cancer. It is an oncology therapeutic developed by Eli Lilly and Company. The drug is currently in clinical development and has not been approved by the FDA.

What does IMC-1121B target?

IMC-1121B is a monoclonal antibody that targets a specific molecular pathway involved in tumor growth. It is being studied in oncology for its potential to treat various cancers, including advanced solid tumors and metastatic malignant melanoma. The drug is designed to interfere with cancer cell signaling to inhibit tumor progression.

Who makes IMC-1121B?

IMC-1121B is developed by Eli Lilly and Company, a pharmaceutical company listed on the stock exchange under the ticker symbol LLY. The drug is an investigational monoclonal antibody in Phase 1 of clinical development for oncology indications, including advanced solid tumors and colorectal carcinoma.

What phase is IMC-1121B in?

IMC-1121B is in Phase 1 of clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities. The drug is being studied for the treatment of advanced solid tumors and other cancers, with clinical trials conducted in the United States, Canada, Spain, and Japan.

What clinical trials is IMC-1121B in?

IMC-1121B has been studied in several clinical trials, including NCT00533702 for metastatic malignant melanoma, NCT00793975 for advanced solid tumors, NCT00862784 for colorectal carcinoma, and NCT01005355 for advanced solid tumors. All trials are completed, with a total enrollment of 280 participants across the studies.

Is IMC-1121B the same as ramucirumab?

IMC-1121B is also known as ramucirumab. It is a monoclonal antibody being developed by Eli Lilly and Company for the treatment of various cancers, including advanced solid tumors and colorectal carcinoma. The drug is in Phase 1 of clinical development and remains investigational.