GEN1029 (HexaBody®-DR5/DR5) Safety Trial in Patients With Malignant Solid Tumors

NCT03576131 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: GCT1029-012017-001394-16236908
• Study Type: interventional
• Target: 48
• Locations: 3 countries
• Sites: 6

Brief Summary

The purpose of the trial is to evaluate the safety of GEN1029 (HexaBody®-DR5/DR5) in a mixed population of patients with specified solid tumors

Conditions

Colorectal Cancer; Non-small Cell Lung Cancer; Triple Negative Breast Cancer; Renal Cell Carcinoma; Gastric Cancer; Pancreatic Cancer; Urothelial Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT criteria in the dose escalation phase of this trial are defined as hematologic toxicity including Grade (G) 4 neutropenia/thrombocytopenia for minimal duration of 7 days, G3/4 febrile neutropenia, \>=G3 thrombocytopenia with bleeding, or G4 anemia; and non-hematologic toxicity including G4 infusion-related reactions (IRR) or anaphylaxis, G3 IRR did not resolve to =\<G1 within 24 hours, \>=G3 diarrhea/vomiting (did not respond to optimal treatment within 2 days), G3 nausea (did not respond to optimal treatment within 7days), or Hy's law or protocol-specified toxicities related to liver function test results or amylase and/or lipase elevations; or any \>=G3 possibly related non-hematological AE, which occurred during first 2 cycles (as specified in protocol).

  From Day 1 to 28 days after the first dose of study drug

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is 'medically important'\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening during the treatment period including the safety follow-up period.

  Day 1 through Day 565 (corresponding to maximum observed duration)

• Number of Participants With >= Grade 3 Laboratory Results

  Number of participants with laboratory measurements of Grade \>= 3 by NCI-CTCAE v4.03 are reported. The NCI-CTCAE is a descriptive terminology is used for AE reporting. The NCI-CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Based on this general guideline: Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death. In case a participant reported multiple severity grades for an AE, only the maximum grade was used.

  Day 1 through Day 565 (corresponding to maximum observed duration)

Secondary Outcomes (15)

• Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05

  Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3

• Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05

  Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3

• Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05

  Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3

• Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05

  Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3

• Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05

  Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3

Study Arms (1)

GEN1029 (HexaBody®-DR5/DR5)

EXPERIMENTAL

Biological: GEN1029 (HexaBody®-DR5/DR5)

Interventions

GEN1029 (HexaBody®-DR5/DR5) BIOLOGICAL

GEN1029 will be administered intravenously. The dose levels will be determined by the starting dose and the escalation steps taken in the trial.

GEN1029 (HexaBody®-DR5/DR5)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced and/or metastatic cancer who have no available standard therapy or who are not candidates for available standard therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN1029 may be beneficial.
• Patient must be ≥ 18 years of age
• Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
• Have an acceptable hematological status
• Have an acceptable renal function
• Have an acceptable liver function
• Have an Eastern Cooperative Oncology Group performance status of 0 or 1
• Body weight ≥ 40kg
• Patients both females and males, of childbearing or reproductive potential must agree to use adequate contraception from screening visit until six months after last infusion of GEN1029

You may not qualify if:

• Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for at least 8 weeks prior to first GEN1029 administration
• Have clinically significant cardiac disease
• Have uncontrolled hypertension as defined in the protocol
• Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke
• History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of Investigational Medicinal Product (IMP)
• Have received a cumulative dose of corticosteroid ≥ 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks before the first GEN1029 administration
• History of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any agent given in the course of this trial
• Radiotherapy within 14 days prior to first GEN1029 administration
• Any prior therapy with a compound targeting DR4 or DR5
• History of chronic liver disease or evidence of hepatic cirrhosis

Sponsors & Collaborators

• Genmab: lead

Study Sites (6)

Yale University

New Haven, Connecticut, 06510, United States

Location

UT M.D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Hospital Univeritario Vall d'Hebron

Barcelona, Spain

Location

START Madrid CIOCC

Madrid, Spain

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, United Kingdom

Location

The Royal Mardsen NHS Foundation Trust

Sutton, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Carcinoma, Renal Cell; Stomach Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Limitations and Caveats

Results of the biweekly dosing regimens are based on the Clinical Study Report.

Results Point of Contact

• Title: Clinical Trial Information
• Organization: Genmab

clinicaltrials@genmab.com

+45 7020 2728

Study Officials

• Ruth Plummer, Professor

  Newcastle Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2018
• First Posted: July 3, 2018
• Study Start: April 30, 2018
• Primary Completion: October 12, 2021
• Study Completion: October 12, 2021
• Last Updated: August 1, 2023
• Results First Posted: December 12, 2022

Record last verified: 2023-07

Locations

US (2); ES (2); GB (2)