A Safety and Efficacy Trial of GEN1046 as Monotherapy and in Combination With Pembrolizumab in Subjects With Recurrent Non-Small Cell Lung cancer

Phase 1

Conditions: Malignant Solid Tumors - Non Small Cell Lung Cancer
MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2021-001928-17-NL

Lead Sponsor: Genmab A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 160

Inclusion Criteria

1. Subject must sign an informed consent form (ICF).
2. Subject must be at least 18 years of age on the day of signing the ICF
3. Subject has 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.
4. Subject must have a tumor PD-L1 expression result available prior to C1D1 demonstrating PD-L1 expression in =1% of tumor cells as assessed by a sponsor designated central laboratory using the Dako PD-L1 IHC 22C3 pharmDx assay (TPS=1%), or per site local assessment with the Dako PD-L1 IHC 22C3 pharmDx assay (TPS=1%) or the VENTANA PD-L1 (SP263) assay (TC =1%) adhering to the manufacturer’s instructions.
Note: Local PD-L1 result needs to be performed on fresh tumor tissue (obtained within 3 months prior to enrollment and after failure/stop of last prior treatment) or, if not feasible, archival tissue (obtained within 12 months prior to enrollment).
5. Subject must have measurable disease per RECIST v1.1 as assessed by the investigator.
6. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) =1.
7. Subject must have life expectancy of at least 3 months.
8. Subject must have adequate organ and bone marrow function.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion Criteria

1. Documentation of known EGFR sensitizing mutations, KRAS, RET, ROS1, or BRAF mutations, NTRK gene infusions, RET rearrangement, ALK gene rearrangements, high-level MET amplification, or METex 14 skipping.
2. Subject has been exposed to any of the following therapies:
- 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 - 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.
3. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients
4. Subject has any of the following:
- Ongoing or active infection requiring intravenous treatment with antiinfective 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.
5. Subject has a known history of any of the following:
- Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy treatment.
- Myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
- Liver disease (eg, alcoholic hepatitis or non-alcoholic steatohepatitis, drug-related or autoimmune hepatitis, or evidence of hepatic cirrhosis).
- 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.
- 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.
For further information, please refer to Clinical Trial Protocol.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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