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