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Safety and Efficacy Study of GEN1046 as a Single Agent or in Combination With Pembrolizumab for Treatment of Recurrent (Non-small Cell) Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05117242
Recruitment Status : Recruiting
First Posted : November 11, 2021
Last Update Posted : May 11, 2023
Sponsor:
Collaborator:
BioNTech SE
Information provided by (Responsible Party):
Genmab

Study Description
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Brief Summary:
The purpose of this trial is to investigate the safety and efficacy of GEN1046 as monotherapy and in combination with pembrolizumab in patients with non-small cell lung cancer who have progressed during or after treatment of previous standard of care

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Metastatic Biological: GEN1046 Biological: Pembrolizumab Phase 2

Detailed Description:
This trial is a randomized, open-label trial evaluating the safety and efficacy of GEN1046 as monotherapy and in combination therapy with pembrolizumab. The trial consists of two parts; a safety phase and an extension phase. The extension phase will be initiated once the safety phase is completed.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Open-Label Trial of GEN1046 as Monotherapy and in Combination Pembrolizumab Therapy in Subjects With Relapsed/Refractory Metastatic Non-Small Cell Lung Cancer After Treatment With Standard of Care Therapy With an Immune Checkpoint Inhibitor
Actual Study Start Date : October 27, 2021
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A
Treatment with GEN1046 once every 21 days for the first 2 cycles and then every 42 days in subsequent cycles
 Biological: GEN1046
GEN1046 will be administered intravenously
Other Name: DuoBody®-PD-L1×4-1BB
Experimental: Arm B
Treatment with GEN1046 + Pembrolizumab once every 21 days
 Biological: GEN1046
GEN1046 will be administered intravenously
Other Name: DuoBody®-PD-L1×4-1BB

Biological: Pembrolizumab
Pembrolizumab will be administered intravenously
Experimental: Arm C
Treatment with GEN1046 + Pembrolizumab once every 42 days
 Biological: GEN1046
GEN1046 will be administered intravenously
Other Name: DuoBody®-PD-L1×4-1BB

Biological: Pembrolizumab
Pembrolizumab will be administered intravenously


Outcome Measures
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Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Throughout the trial until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months) ]
    ORR will be measured as the proportion of subjects with a confirmed response of complete response (CR) or partial response (PR) as per RECIST v1.1


Secondary Outcome Measures :
  1. Duration of response (DOR) [ Time Frame: From onset date of response until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months) ]
    DOR will be measured as the time from initial onset of CR or PR to first radiographic progression as per RECIST v. 1.1 or death from any cause, whichever occurs first.

  2. Time to response (TTR) [ Time Frame: From first treatment to date of onset of initial response (CR or PR) as per RECIST v.1.1 (an expected average of 6 months) ]
    TTR will be measured as the time from first treatment to onset of initial response (CR or PR) as per RECIST v.1.1

  3. Progression-free survival (PFS) [ Time Frame: From first treatment to first documented progression or death due to any cause (an expected average of 6 months) ]
    PFS will be measured from date of first treatment until date of radiographic progression as per RECIST v.1.1 or until death from any cause, whichever occurs first

  4. Overall survival (OS) [ Time Frame: From first treatment to date of death (assessed up to 3 years after the last participant's first dose in the trial) ]
    Defined as time to death from of any cause

  5. Incidence and severity of adverse events (AEs) and laboratory abnormalities [ Time Frame: Throughout the trial until end of safety follow-up period (60 days or 90 days after last dose) ]
    Incidence of treatment-emergent AEs as assessed by CTCAE v5.0. Laboratory parameters graded by CTCAE v5.0


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Have signed an informed consent form (ICF)
  • Be at least 18 years of age.
  • Have histologically or cytologically confirmed diagnosis of stage 4 NSCLC with at least 1 prior line of systemic therapy containing an anti-PD-1/PD-L1 mAb for metastatic disease
  • Have a tumor PD-L1 expression result available prior to first treatment demonstrating PD-L1 expression in ≥1% of tumor cells as assessed by a central or local laboratory during screening.
  • Have measurable disease per RECIST v1.1.
  • Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
  • Have life expectancy of at least 3 months.
  • Have adequate organ and bone marrow function as defined in the protocol.

Key Exclusion Criteria:

  • Documentation of known EGFR, KRAS, RET, ROS1, BRAF mutations, NTRK gene infusions, RET arrangement, ALK gene rearrangements, high-level MET amplification, or METex 14 skipping. Note: Subjects harboring such mutations, gene rearrangements or amplifications may be enrolled in the trial, if subjects have received prior approved targeted therapy for such mutations, the subject may still be eligible for this trial.
  • Treatment with an anti-cancer agent within 28 days prior to GEN1046 administration.
  • Any investigational agent for the treatment of stage 4 NSCLC.
  • Radiotherapy within 14 days prior to first GEN1046 administration or received lung radiation therapy of >30 Gy within 6 months of the first dose of trial treatment. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
  • Chronic systemic immunosuppressive corticosteroid doses, ie, prednisone >10 mg daily or a cumulative dose >150 mg prednisone within 14 days before the first GEN1046 administration.
  • Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Subject has contraindications to the use of pembrolizumab per local prescribing information.
  • Subject has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis (interstitial lung disease).
  • Ongoing or active infection requiring intravenous treatment with anti-infective therapy that has been administered <2 weeks prior to first dose.
  • 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 (within 6 months) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs.

  • Subject has a known history of any of the following:

    1. Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy treatment.
    2. Myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
    3. Liver disease (eg, alcoholic hepatitis or non-alcoholic steatohepatitis, drug-related or autoimmune hepatitis, or evidence of hepatic cirrhosis).
    4. 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.
    5. Grade 3 or higher 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05117242


Contacts
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Contact: Genmab A/S Trial Information +45 70202728 clinicaltrials@genmab.com

Locations
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Sponsors and Collaborators
Genmab
BioNTech SE
More Information
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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT05117242    
Other Study ID Numbers: GCT1046-04
2021-001928-17 ( EudraCT Number )
First Posted: November 11, 2021    Key Record Dates
Last Update Posted: May 11, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Genmab:
DuoBody®
Bispecific antibody
PD-L1
4-1BB
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
 Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action