Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Ramucirumab

Sorafenib

Angiogenesis Inhibitors

Growth Inhibitors

Placebo

8 milligrams/kilogram (mg/kg) intravenous (IV) every 2 weeks

Ramucirumab DP (IMC-1121B)

Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

This is a Phase 3 multicenter, randomized study evaluating the safety and efficacy of ramucirumab DP plus BSC as a double-blind, placebo-controlled (placebo plus BSC) comparison.

Approximately 544 participants, at least 18 years of age, with Child-Pugh score \< 7 and diagnosed with hepatocellular carcinoma will be randomized. Participants must have received sorafenib as first-line systemic treatment for hepatocellular carcinoma (HCC), and must have discontinued sorafenib prior to entering the study.

Hypothesis: This sample size will allow differentiation of the expected increase in median overall survival (OS), from 8 months in the placebo arm to 10.67 months in the ramucirumab arm.

Upon registration and completion of screening procedures, eligible participants with HCC who have disease progression during or following first-line therapy with sorafenib, or were intolerant to this agent, will be randomized to receive either ramucirumab DP or placebo.

The treatment regimen will be continued until radiographic or symptomatic progression, the development of unacceptable toxicity, noncompliance or withdrawal of consent by the participant, or investigator decision.

A Study of Ramucirumab (IMC-1121B) Drug Product (DP) and Best Supportive Care (BSC) Versus Placebo and BSC as 2nd-Line Treatment in Participants With Hepatocellular Carcinoma After 1st-Line Therapy With Sorafenib

A Multicenter, Randomized, Double-Blind, Phase 3 Study of Ramucirumab (IMC-1121B) Drug Product and Best Supportive Care (BSC) Versus Placebo and BSC as Second-Line Treatment in Patients With Hepatocellular Carcinoma Following First-Line Therapy With Sorafenib (REACH)

OS was defined as the time from the date of randomization to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up were censored on the last date the participant was known to be alive.

PFS was defined as time from date of randomization until date of objectively determined progressive disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or death from any cause. PD was defined as ≥20% increase in sum of diameters (SOD) of target lesions, taking as reference smallest sum on study (including baseline sum if it was smallest). Sum must show a ≥5 millimeter (mm) increase. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. In primary analysis, participants alive and without PD were censored at day of last adequate tumor assessment; progression or deaths without progression occurring immediately after ≥2 missed tumor assessments, were censored at day of the last adequate tumor assessment prior to missing assessments; participants who began new anticancer therapy were censored at day of the last adequate tumor assessment prior to start of new anticancer therapy.

ORR was defined, using RECIST v1.1 criteria, as the percentage of participants who achieved a best overall response of CR or PR. CR was defined as the disappearance of all lesions and any intratumor arterial enhancement in target lesions, the normalization of the tumor marker level and all lymph nodes short axis reduced to \<10 mm. PR was defined as ≥30% decrease in the SOD of target lesions, including the short axes of any target lymph nodes, taking as reference the baseline SOD of target lesions, no new lesions and stable nontarget lesions. Percentage of participants was calculated as: (number of participants with CR or PR / number of participants randomized) \* 100.

TTP was defined as the time from randomization to the first radiographically documented PD. PD was defined, using RECIST v1.1 criteria, as ≥20% increase in SOD of target lesions, taking as reference smallest sum on study (including baseline sum if it was the smallest). Sum must show an absolute increase of ≥5 mm. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. Participants without PD were censored at the day of the last adequate tumor assessment. Progression occurred immediately after ≥2 missed tumor assessments and were censored at the day of the last adequate tumor assessment prior to the missing assessments. Participants who began new anticancer therapy were censored at the day of their last adequate tumor assessment prior to start of new anticancer therapy.

The FHSI-8 is a self-administered 8-item questionnaire that measures a participant's symptoms in the domains of jaundice, stomach pain/discomfort weight loss, and fatigue. Participants rated each item on a 5-point scale from 0 (not at all) to 4 (very much). Item scores were calculated as outlined in the FACIT manual. FHSI-8 total score was the sum of each item's score with a total score ranging from 0 (highly symptomatic) to 32 (asymptomatic).

The EQ-5D is a self-reported, 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire related to the participant's current health state. Each question was scored using a 3 level scale (no problems, some problems, or extreme problems). EQ-5D health state was defined by combining responses from each of the 5 dimensions into a weighted health-state index score according to the United Kingdom (UK) population based algorithm where 0 = death and 1 = perfect health.

The number of participants with serious AEs (SAEs), other non-serious AEs and participants who died. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Participants were considered positive for anti-ramucirumab antibodies \[anti-drug antibodies (ADA)\] if the post-treatment sample had an increase of at least 4-fold in titer from the pretreatment values. If the pretreatment value was not detected or was not present, a 1:20 post-treatment titer was required to indicate treatment emergence of ADA.

Eli Lilly and Company

Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.

Ramucirumab (IMC-1121B) + BSC

Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.

Placebo + BSC

Total

Age, Continuous

<65 years

≥65 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Portugal

Philippines

Taiwan

Hong Kong

Spain

Thailand

Israel

Switzerland

Italy

France

Australia

Netherlands

Korea, Republic of

Finland

Austria

Czech Republic

Hungary

Canada

Belgium

Brazil

Romania

Bulgaria

Germany

Norway

Japan

Sweden

Region of Enrollment

Chief Medical Officer

Intent-to-treat (ITT) Population: All randomized participants. Participants censored: Ramucirumab+BSC (Ram)=65, Placebo+BSC (Pl)=58.

Overall Survival (OS)

ITT Population: All randomized participants. Participants censored: Ram=43, Pl=19.

Progression-Free Survival (PFS)

ITT Population: All randomized participants.

Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

ITT Population: All randomized participants. Participants censored: Ram=86, Pl=52.

Time to Radiographic Progression (TTP)

Cycle 4 (n=166, 147)

Cycle 10 (n=70, 45)

Cycle 16 (n=47, 24)

End of Treatment (n=169, 199)

Randomized participants who had FHSI-8 at baseline and the specified time points.

Change From Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)

Cycle 4 (n=166, 145)

Cycle 10 (n=71, 45)

Cycle 16 (n=47, 25)

End of Treatment (n=166, 190)

Randomized participants who had an EQ-5D score at baseline and the specified time points.

Change From Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score

SAEs

Other Non-SAEs

Died

Participants who received at least 1 dose of study drug.

Number of Participants With Adverse Events (AEs) and the Number of Participants Who Died

Participants who received Cycle 1 of Ram and had Cmax results.

Maximum Concentration (Cmax) of Ramucirumab, Cycle 1

Participants who received Cycle 4 of Ram and had Cmax results.

Cmax of Ramucirumab, Cycle 4

Participants who received Cycle 7 of Ram and had Cmax results.

Cmax of Ramucirumab, Cycle 7

Participants who received at least 1 dose of study drug and had post-treatment ADA analysis.

Number of Participants With Treatment Emergent Positive Anti-Ramucirumab Response [Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)]

Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) intravenous (IV) infusion every 2 weeks.

Best supportive care (BSC): Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.

Spots Global Cancer Trial Database for subclass 1 (igg1) monoclonal antibody (mab)