NCT01335009

Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma

Completed Phase 2 Results posted Last updated 1 September 2021

What this trial tests

Phase 2 trial testing MORAb-004 (monoclonal antibody) in Metastatic Melanoma in 76 participants. Completed in 10 April 2020.

Timeline

16 May 2011

Primary endpoint
2 December 2013

10 April 2020

Quick facts

Lead sponsor	Eisai Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	76
Start date	16 May 2011
Primary completion	2 December 2013
Estimated completion	10 April 2020
Sites	29 locations across United Kingdom, Germany, United States, Australia

Drugs / interventions tested

• MORAb-004 (monoclonal antibody) — full drug profile →

Conditions studied

• Metastatic Melanoma — all drugs for Metastatic Melanoma →

Sponsor

Eisai Inc. — full company profile →

Who can join

18 and older, any sex, with Metastatic Melanoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Progression-free Survival (PFS) at Week 24 Primary · Week 24

PFS was defined as the time (in weeks) from the date of randomization to the date of the first sign of disease progression (PD) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or date of death, regardless of cause. PD greater than or equal to (\>=) 20 percent (%) increase in the nadir of total tumor burden (TTB) (minimum 5 millimeter \[mm\]). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received a new anti-cancer therapy before disease progression had their PFS time

Group	Value	95% CI
MORAb-004 2 mg/kg	13.5	5.0 – 26.4
MORAb-004 4 mg/kg	8.9	2.3 – 21.3

Percentage of Participants With PFS at Weeks 16 and 52 Secondary · Week 16 and Week 52

PFS was defined as the time (in weeks) from the date of randomization to the date of the first observation of PD (RECIST version 1.1) or date of death, regardless of the cause. PD \>=20% increase in the nadir of TTB (minimum 5 mm). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was initiated. PFS was based on the Kaplan-Meier method.

Week 16

Group	Value	95% CI
MORAb-004 2 mg/kg	32.5	18.3 – 47.6
MORAb-004 4 mg/kg	20.8	9.2 – 35.7

Week 52

Group	Value	95% CI
MORAb-004 2 mg/kg	NA	NA – NA
MORAb-004 4 mg/kg	8.9	2.3 – 21.3

Overall Survival (OS) Secondary · Date of first study treatment (Day 1) to date of death or up to approximately 2 years 7 months

OS was defined as the time (in weeks) from the date of randomization to the date of death, regardless of cause. In the absence of death confirmation, or for participants alive at the time of analysis, the survival time was censored at the date of the last study follow-up. OS was calculated using the Kaplan-Meier method. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).

Group	Value	95% CI
MORAb-004 2 mg/kg	40.9	29.0 – 53.3
MORAb-004 4 mg/kg	29.3	22.9 – 35.4

Percentage of Participants With Overall Response Secondary · Date of first study treatment (Day 1) to complete response or partial response, assessed up to approximately 2 years 7 months

ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) that occurred (defined by RECIST version 1.1) using CT/MRI. Per RECIST 1.1, CR= disappearance of all lesions; PR greater than or equal to (\>=) 30percent (%) decrease from baseline in TTB. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).

Group	Value	95% CI
MORAb-004 2 mg/kg	NA	NA – NA
MORAb-004 4 mg/kg	3.1	0.0 – 9.2

Optimal Biologic Dosing (OBD) of Morab-004 Secondary · Day 1 Cycle 1 (Cycle length = 28 days)

OBD is defined as the dose level/exposure level at which three parameters are met: 1) adequate pharmacokinetic (PK) profile with a serum half-life (t1/2) of \>=48 hours, 2) at least minimal demonstration of antitumor efficacy (50% or greater PFS rate at 16 weeks), and 3) change of 25% or greater from baseline value in any of the pharmacodynamic (PD) parameters assessed in the study in 30% of participants at that dose level.

Group	Value	95% CI
MORAb-004 2 mg/kg	NA
MORAb-004 4 mg/kg	NA

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug to 45 days after the last dose of study drug (up to approximately 8 years 11 months). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MORAb-004 2 mg/kg

Serious: 17/40 (43%)

Deaths: 28/40

MORAb-004 4 mg/kg

Serious: 16/36 (44%)

Deaths: 32/36

Serious adverse events (40 terms)

Reaction	System	MORAb-004 2 mg/kg	MORAb-004 4 mg/kg
Metastatic malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Cellulitis	Infections and infestations	—	—
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Infusion related reaction	General disorders	—	—
Pyrexia	General disorders	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Neuroendocrine carcinoma of the skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Sepsis	Infections and infestations	—	—
Septic shock	Infections and infestations	—	—
Urosepsis	Infections and infestations	—	—
Wound infection	Infections and infestations	—	—
Chills	General disorders	—	—
Fatigue	General disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Bradycardia	Cardiac disorders	—	—
Pericardial effusion	Cardiac disorders	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—
Brain oedema	Nervous system disorders	—	—

Other adverse events (209 terms — click to expand)

Reaction	System	MORAb-004 2 mg/kg	MORAb-004 4 mg/kg
Headache	Nervous system disorders	—	—
Fatigue	General disorders	—	—
Chills	General disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—
Infusion related reaction	General disorders	—	—
Oedema peripheral	General disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Dizziness	Nervous system disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	—	—
Anxiety	Psychiatric disorders	—	—
Confusional state	Psychiatric disorders	—	—
Influenza like illness	General disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Upper respiratory tract infection	Respiratory, thoracic and mediastinal disorders	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—
Hypertension	Vascular disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—
Tremor	Nervous system disorders	—	—
Cellulitis	Infections and infestations	—	—
Night sweats	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Metastatic malignant melanoma, Cellulitis, Malignant neoplasm progression, Infusion related reaction, Pyrexia, Pulmonary embolism, Anaemia, Neuroendocrine carcinoma of the skin.

Data from ClinicalTrials.gov NCT01335009 adverse events section.

Sponsor's own description

This is a global, Phase 2, open label, dose selection, proof-of-concept study to assess progression free survival in subjects with metastatic melanoma.

Approximately 80 subjects at 29 sites in the U.S., U.K., Germany and Australia will be randomized into one of two dose groups: 2 mg/kg, 4 mg/kg. Weekly treatment will continue until disease progression.

Subjects must have measurable disease by CT Scan or MRI and must have completed at least one prior round of chemotherapy.

Subjects will be assessed for Efficacy, PK/PD, Overall survival, and Safety (Adverse Events/Adverse Events of Interest, Electrocardiograms (ECG's), clinical labs, physical exams/vital signs, tolerability).

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. CD248: A therapeutic target in cancer and fibrotic diseases.
   Teicher BA. · · 2019 · cited 56× · PMID 30847027 · DOI 10.18632/oncotarget.26590
2. The role of angiogenesis in melanoma: Clinical treatments and future expectations.
   Wu Z, Bian Y, Chu T, Wang Y, et al · · 2022 · cited 25× · PMID 36588679 · DOI 10.3389/fphar.2022.1028647