First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1046 in Subjects With Malignant Solid Tumors

INTRODUCTION

  • Org Study ID: GCT1046-01
  • Secondary ID: 2018-003402-63
  • NTC ID: NCT03917381
  • Sponsor: Genmab

BRIEF SUMMARY

The purpose of the trial is to evaluate the safety of GEN1046 as monotherapy and in combination therapies in patients with malignant solid tumors

DETAILED DESCRIPTION

The trial is an open-label, multi-center safety trial of GEN1046. The trial consists of two parts, a dose escalation part (phase 1, first-in-human (FIH) and an expansion part (phase 2a)). The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined.

  • Overall Status
    Recruiting
  • Start Date
    May 14, 2019
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Dose limiting toxicity (DLT)

Primary Outcome 1 - Timeframe: DLTs are assessed during the first cycle (21 days) in each cohort]

Primary Outcome 2 - Measure: Adverse events

Primary Outcome 2 - Timeframe: throughout the study and up to 2 months after last subject last treatment

Primary Outcome 3 - Measure: Safety laboratory parameters (hematology, biochemistry, coagulation, endocrines)

Primary Outcome 3 - Timeframe: throughout the study and up to 2 months after last subject last treatment

Primary Outcome 4 - Measure: For expansion cohort 1 only: Objective Response Rate (ORR)

Primary Outcome 4 - Timeframe: throughout the study and up to 2 months after last subject last treatment

CONDITION

  • Solid Tumors
  • Non-small Cell Lung Cancer
  • Urothelial Carcinoma
  • Endometrial Carcinoma
  • Triple Negative Breast Cancer
  • Squamous Cell Carcinoma of the Head and Neck
  • Cervical Cancer

ELIGIBILITY

Key Inclusion Criteria:
For Dose Escalation:
• Have a histologically or cytologically confirmed non-CNS solid tumor that is metastatic or unresectable and for whom there is no available standard therapy
For Expansion:
• Have histologically or cytological confirmed diagnosis of relapsed or refractory, advanced and/or metastatic NSCLC, EC, UC, TNBC, SCCHN, or cervical cancer who are not anymore candidates for standard therapy For two separate expansion cohorts: metastatic NSCLC without prior systemic treatment regimens for metastatic disease.
For Both Dose Escalation and Expansion
Have measurable disease according to RECIST 1.1

- Have Eastern Cooperative Oncology Group (ECOG) 0-1

- Have an acceptable hematological status

- Have acceptable liver function

- Have an acceptable coagulation status

- Have acceptable renal function
Key Exclusion Criteria:
Have uncontrolled intercurrent illness, including but not limited to:
Ongoing or active infection requiring intravenous treatment with antiinfective therapy

- Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia

- Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg, despite optimal medical management

- Ongoing or recent evidence of autoimmune disease

- History of irAEs that led to prior checkpoint treatment discontinuation

- Prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade

- History of chronic liver disease or evidence of hepatic cirrhosis

- History of non-infectious pneumonitis that has required steroids or currently has pneumonitis

- 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 GEN1046

- Serious, non-healing wound, skin ulcer (of any grade), or bone fracture

- Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke
Prior therapy:
Radiotherapy: Radiotherapy within 14 days prior to first GEN1046 administration. Palliative radiotherapy will be allowed.

- Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1046 administration. Accepted exceptions are bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab

- Toxicities from previous anti-cancer therapies that have not adequately resolved
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: +4570202728

Email: clinicaltrials@genmab.com

LOCATION

Facility Status Contact
Facility: Mayo Clinic
Phoenix, Arizona 85054
United States
Status: Recruiting Contact: Contact
Clinical Trials Referral Office
855-776-0015
Facility: Yale University Cancer Center
New Haven, Connecticut 06520-8028
United States
Status: Recruiting Contact: Contact
Cassandra Moore, Dr.
855-776-0015
Facility: Mayo Clinic
Jacksonville, Florida 32224
United States
Status: Recruiting Contact: Contact
Patricia M LoRusso
855-776-0015
Facility: Emory University
Atlanta, Georgia 30322
United States
Status: Recruiting Contact: Contact
Clinical Trials Referral Office

Facility: University of Iowa Hospitals
Iowa City, Iowa 52242
United States
Status: Recruiting Contact: Contact
Yanyan Lou, Dr.

Facility: Norton Healthcare Inc
Louisville, Kentucky 40202
United States
Status: Recruiting Contact: Contact
Suresh Ramalingam

Facility: University of Michigan
Ann Arbor, Michigan 48109
United States
Status: Recruiting Contact: Contact
Muhammed Furqan

Facility: START Midwest
Grand Rapids, Michigan 49546
United States
Status: Recruiting Contact: Contact
John Hamm

Facility: Mayo Clinic
Rochester, Minnesota 55905
United States
Status: Recruiting Contact: Contact
Erin Cobain

Facility: Washington University School of Medicine
Saint Louis, Missouri 63110
United States
Status: Recruiting Contact: Contact
Manish Sharma

Facility: NYU Langone
New York, New York 10016
United States
Status: Recruiting Contact: Contact
Clinical Trials Referral Office

Facility: UNC Chapel Hill
Chapel Hill, North Carolina 27514
United States
Status: Recruiting Contact: Contact
Ashish Chintakuntlawar, Dr.

Facility: Levine Cancer Institute, Atrium Health
Charlotte, North Carolina 28204
United States
Status: Recruiting Contact: Contact
Jeffrey Ward

Facility: University Hospitals Cleveland Medical Center
Cleveland, Ohio 44106
United States
Status: Recruiting Contact: Contact
Daniel Cho

Facility: University Hospital Brno
Brno, 12000
Czechia
Status: Recruiting Contact: Contact
Jared Weiss

Facility: Fakultni nemocnice Olomouc
Olomouc, 64239
Czechia
Status: Recruiting Contact: Contact
Daniel Haggstrom

Facility: Onkologiai Klinika
Debrecen, 52621
Hungary
Status: Recruiting Contact: Contact
Alberto Montero

Facility: BKMK Hospital
Kecskemét, 08035
Hungary
Status: Recruiting Contact: Contact
Zdenek Kral

Facility: Pulmonology Hospital Törökbálinti
Törökbálint, 28040
Hungary
Status: Recruiting Contact: Contact
Bohuslav Melichar

Facility: Rambam Health Care Campus RHCC - Rambam Medical Center
Haifa, 28041
Israel
Status: Recruiting Contact: Contact
Peter Arkosy

Facility: Hadassah Medical Organization HMO - Sharett Institute of Oncology
Jerusalem, 28050
Israel
Status: Recruiting Contact: Contact
Judit Kocsis

Facility: Tel Aviv Sourasky Medical Center
Tel Aviv, 31008
Israel
Status: Recruiting Contact: Contact
Gabriella Galffy

Facility: Sheba Medical Center, Ramat Gan
Tel HaShomer, 46010
Israel
Status: Recruiting Contact: Contact
Corinne Maurice-Dror

Facility: IRCCS - Istituto Europeo di Oncologia IEO
Milan,
Italy
Status: Recruiting Contact: Contact
Tamar Peretz Yablonski

Facility: Istituto Nazionale Tumori - Fondazione Pascale Italy
Napoli,
Italy
Status: Recruiting Contact: Contact
Ravit Geva

Facility: AUSL Romagno-Ravenna
Ravenna,
Italy
Status: Recruiting Contact: Contact
Eytan Ben-Ami

Facility: Policlinico Uni. Campus Bio-Medico
Roma,
Italy
Status: Recruiting Contact: Contact
Giuseppe Curigliano

Facility: Regina Elena National Cancer Institute
Rome,
Italy
Status: Recruiting Contact: Contact
Paolo Ascierto

Facility: Uniwersyteckie Centrum Kliniczne
Gdańsk,
Poland
Status: Recruiting Contact: Contact
Manolo D'Arcangelo

Facility: Dom Lekarski SA
Szczecin,
Poland
Status: Recruiting Contact: Contact
Giuseppe Tonini

Facility: Maria Sklodowska Curie National Research Instutute of Oncology
Warsaw,
Poland
Status: Recruiting Contact: Contact
Federico Cappuzzo

Facility: Medpolonia Sp. z o.o.
Wielkopolskie,
Poland
Status: Recruiting Contact: Contact
Jacek Jassem

Facility: Hospital Universitario Vall dHebron
Barcelona,
Spain
Status: Recruiting Contact: Contact
Piotr Serwatowski

Facility: START Madrid-FJD, Hospital Fundación Jiménez Díaz
Madrid,
Spain
Status: Recruiting Contact: Contact
Iwona Lugowska

Facility: Hospital Universitario 12 de Octubre
Madrid,
Spain
Status: Recruiting Contact: Contact
Rodryg Ramlau

Facility: START Madrid-CIOCC
Madrid,
Spain
Status: Recruiting Contact: Contact
Elena Garralda Cabanas

Facility: Hospital Universitario La Princesa
Madrid,
Spain
Status: Recruiting Contact: Contact
Victor Moreno

Facility: MD Anderson Cancer Center Madrid
Madrid,
Spain
Status: Recruiting Contact: Contact
Santiago Ponce

Facility: Hospital Universitario Virgen de la Victoria
Málaga,
Spain
Status: Recruiting Contact: Contact
Emiliano Calvo

Facility: Clinica Universidad de Navarra
Pamplona,
Spain
Status: Recruiting Contact: Contact
Ramon Colomer

Facility: Hospital Clinico De Valencia
Valencia,
Spain
Status: Recruiting Contact: Contact
Enrique Grande Pulido