A Safety and Efficacy Trial of GEN1046 as Monotherapy and in Combination With Anti-cancer Therapy 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-IT
• Lead Sponsor: GENMAB A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-11-10
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

1. Subject must sign an informed consent form (ICF).
2. Subject must be at least 18 years of age.
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 PD-L1 tumor expression score of TPS >/=1%assessed by a central laboratory during screening.
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) 7. Subject must have life expectancy of at least 3 months.
8. Subject must have adequate organ and bone marrow function as defined in protocol.
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 66
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66

Exclusion Criteria

1. Documentation of known EGFR, ROS1, or ALK mutations or gene rearrangements. Additionally, the statues of BRAF, METex 14 skipping, KRAS mutations, RET rearrangement, high-level MET amplification, or NTRK gene infusions will be required.
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 a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
5. 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.
6. 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