Trial Outcomes & Findings for A Study of Ramucirumab (LY3009806) Given by Injection Under the Skin in Participants With Advanced Cancer (NCT NCT04557384)

NCT ID: NCT04557384

Last Updated: 2023-02-27

Results Overview

PK: AUC of Ramucirumab over the dosing interval was evaluated. Cycle = 21 days.

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 3 participants
• Primary outcome timeframe: Cycle (C) 1 Day (D) 1:Predose; C1D2:24 hours (h) postdose;C1D4:48-96 h postdose;C1D8:predose;C1D15:predose;C1D18:48-96 h postdose;C2D1:predose;C2D8:predose;C2D11:48-96h postdose;C3D1:predose
• Results posted on: 2023-02-27

Participant Flow

Completers included participants who had progressive disease, off protocol therapy due to toxicity and having completed the short-term follow-up, death due to any cause.

Participant milestones

Measure	Ramucirumab Participants received starting dose of 700 milligram (mg) ramucirumab loading dose (LD) subcutaneously (SC) followed, a week later, by 350 mg ramucirumab maintenance dose (MD) administered SC once a week.
Overall Study STARTED	3
Overall Study Received At Least 1 Dose of Study Drug	3
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Ramucirumab Participants received starting dose of 700 milligram (mg) ramucirumab loading dose (LD) subcutaneously (SC) followed, a week later, by 350 mg ramucirumab maintenance dose (MD) administered SC once a week.
Overall Study Study Terminated by Sponsor	1
Overall Study Death	1

Baseline Characteristics

A Study of Ramucirumab (LY3009806) Given by Injection Under the Skin in Participants With Advanced Cancer

Baseline characteristics by cohort

Measure	Ramucirumab n=3 Participants Participants received starting dose of 700 mg ramucirumab LD, SC followed, a week later, by 350 mg ramucirumab MD administered SC once a week.
Age, Continuous	66.67 years STANDARD_DEVIATION 5.508 • n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	3 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants
Race (NIH/OMB) White	2 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	3 Participants n=93 Participants

PRIMARY outcome

Timeframe: Cycle (C) 1 Day (D) 1:Predose; C1D2:24 hours (h) postdose;C1D4:48-96 h postdose;C1D8:predose;C1D15:predose;C1D18:48-96 h postdose;C2D1:predose;C2D8:predose;C2D11:48-96h postdose;C3D1:predose

Population: All participants who received at least 1 dose of study drug and had evaluable PK data.

PK: AUC of Ramucirumab over the dosing interval was evaluated. Cycle = 21 days.

Outcome measures

Measure	Ramucirumab n=3 Participants Participants received starting dose of 700 mg ramucirumab LD, SC followed, a week later, by 350 mg ramucirumab MD administered SC once a week.
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Ramucirumab	NA nanograms*hours/milliliter (ng*hr/mL) Geometric Coefficient of Variation NA Data were too limited (below the limit of quantification in concentration) and AUC summary was not able to be calculated.

PRIMARY outcome

Timeframe: C1D1:Predose; C1D2:24 hours (h) postdose;C1D4:48-96 h postdose;C1D8:predose;C1D15:predose;C1D18:48-96 h postdose;C2D1:predose;C2D8:predose;C2D11:48-96h postdose;C3D1:predose

Population: All participants who received at least 1 dose of study drug and had evaluable PK data.

PK: Cmax of Ramucirumab was evaluated.

Outcome measures

Measure	Ramucirumab n=3 Participants Participants received starting dose of 700 mg ramucirumab LD, SC followed, a week later, by 350 mg ramucirumab MD administered SC once a week.
PK: Maximum Concentration (Cmax) of Ramucirumab	NA nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA Data were too limited (below the limit of quantification in concentration) and Cmax was not able to be calculated.

PRIMARY outcome

Timeframe: C1D8: predose; C1D15: predose; C2D1: predose; C2D8: predose; C3D1: predose

Population: All participants who received at least 1 dose of study drug and had evaluable PK data.

Ctrough of Ramucirumab was evaluated.

Outcome measures

Measure	Ramucirumab n=3 Participants Participants received starting dose of 700 mg ramucirumab LD, SC followed, a week later, by 350 mg ramucirumab MD administered SC once a week.
PK: Serum Trough Concentration (Ctrough) of Ramucirumab C1D8	12.6 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 79
PK: Serum Trough Concentration (Ctrough) of Ramucirumab C1D15	20.9 microgram per milliliter (µg/mL) Geometric Coefficient of Variation 41.6
PK: Serum Trough Concentration (Ctrough) of Ramucirumab C2D1	NA microgram per milliliter (µg/mL) Geometric Coefficient of Variation NA For n = 1, Individual value = 28.4
PK: Serum Trough Concentration (Ctrough) of Ramucirumab C2D8	NA microgram per milliliter (µg/mL) Geometric Coefficient of Variation NA For n = 1, Individual value = 38.3
PK: Serum Trough Concentration (Ctrough) of Ramucirumab C3D1	NA microgram per milliliter (µg/mL) Geometric Coefficient of Variation NA For n = 1, Individual value = 34.6

SECONDARY outcome

Timeframe: C1D1: predose; C1D15: predose; C2D8: predose; C4D1: predose

Population: Zero participants were analyzed. Data not collected.

Percentage of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1, Cycle 2, Cycle 3: D1, D8, D15, D22: 5-15 min, 60 min post injection; C1D2: 24 hours (h) post injection; C1D4 (± 1 day)

Population: All randomized participants who received at least one dose of study drug and had at least one post dose safety assessment.

The number of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Measure	Ramucirumab n=3 Participants Participants received starting dose of 700 mg ramucirumab LD, SC followed, a week later, by 350 mg ramucirumab MD administered SC once a week.
Number of Participants With Injection Site Reactions (ISRs)	1 participants

Adverse Events

Ramucirumab

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Measure	Ramucirumab n=3 participants at risk Participants received starting dose of 700 mg ramucirumab LD, SC followed, a week later, by 350 mg ramucirumab MD administered SC once a week.
Gastrointestinal disorders Pancreatitis acute	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
General disorders Asthenia	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.

Other adverse events

Measure	Ramucirumab n=3 participants at risk Participants received starting dose of 700 mg ramucirumab LD, SC followed, a week later, by 350 mg ramucirumab MD administered SC once a week.
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 2 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dyspepsia	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 2 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Pancreatitis	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Pancreatitis acute	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 2 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
General disorders Fatigue	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
General disorders Generalised oedema	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Portal vein thrombosis	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fall	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Investigations Lipase increased	33.3% 1/3 • Number of events 3 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Investigations Weight decreased	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Investigations Weight increased	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	66.7% 2/3 • Number of events 2 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Confusional state	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Vascular disorders Embolism	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Vascular disorders Flushing	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	33.3% 1/3 • Number of events 1 • Up To 40 Days All randomized participants who received at least 1 dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place