Safety and Efficacy Study of GEN1046 as a Single Agent or in Combination With Another Anti-cancer Therapy for Treatment of Recurrent (Non-small Cell) Lung Cancer
Study Details
Study Description
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 failed previous standard of care.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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
Arms and Interventions
| 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 Names:
|
| Experimental: Arm B Treatment with GEN1046 + Pembrolizumab once every 21 days |
Biological: GEN1046
GEN1046 will be administered intravenously
Other Names:
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 Names:
Biological: Pembrolizumab
Pembrolizumab will be administered intravenously
|
Outcome Measures
Primary Outcome Measures
- Objective response rate (ORR) [The objective response rate will be assessed from first treatment until 6 months after last subjects first treatment]
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
- Duration of response [Duration of response will be assessed from first treatment until 6 months after last subjects first treatment]
Duration of response will be measured as the time from initial onset of confirmed response (CR or PR) to first radiographic progression as per RECIST v. 1.1 or death from any cause, whichever occurs first.
- Time to response [Time to response will be assessed from first treatment until 6 months after last subjects first treatment]
Time to response will be measured as the time from first treatment to onset of initial response (CR or PR) as per RECIST v.1.1
- Progression-free survival [Progression-free survival will be assessed from first treatment until 6 months after last subjects first treatment]
Progression-free survival 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
- Overall survival [Overall survival will be assessed from first treatment until 6 months after last subjects first treatment]
Overall survival will be measured from date of first treatment until death from any cause
- Incidence and severity of adverse events and laboratory abnormalities [Adverse events and safety laboratory data are collected from first treatment until 6 months after last subjects first treatment]
Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0. Laboratory parameters graded by CTCAE v5.0
Eligibility Criteria
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
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Have PD-L1 tumor expression score of TPS ≥1% assessed by a central laboratory during screening.
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Have measurable disease per RECIST v1.1.
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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, ROS1, or ALK mutations or gene rearrangements.
-
Treatment with an anti-cancer agent within 28 days prior to GEN1046 administration.
-
Any investigational agent for the treatment of stage 4 NSCLC.
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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.
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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).
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Ongoing or active infection requiring intravenous treatment with anti-infective therapy that has been administered <2 weeks prior to first dose.
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Symptomatic congestive heart failure (grade III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia.
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Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management.
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Ongoing or recent (within 6 months) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs.
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Subject has a known history of any of the following:
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Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy treatment.
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Myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
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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.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | St. Joseph Heritage Healthcare | Santa Rosa | California | United States | 95403 |
| 2 | Florida Cancer Specialists - FCS South | Fort Myers | Florida | United States | 33901 |
| 3 | Florida Cancer Center | Saint Petersburg | Florida | United States | 33705 |
| 4 | Cancer & Hematology Centers of Western Michigan CHCWM P.C. | Grand Rapids | Michigan | United States | 49503 |
| 5 | Oncology Clinical Trials Ascension Providence Hospital | Southfield | Michigan | United States | 48075 |
| 6 | Erasmus MC | Rotterdam | Netherlands | ||
| 7 | Med Polonia Sp. z o.o. | Poznań | Poland | ||
| 8 | Szpital Specjalistyczny w Prabutach Sp. z o.o. | Prabuty | Poland | ||
| 9 | Hospital Universitari Vall dHebron | Barcelona | Spain | ||
| 10 | Clinica Universidad de Navarra CUN | Madrid | Spain | ||
| 11 | Hospital Universitario 12 de Octubre | Madrid | Spain | ||
| 12 | Hospital Universitario Fundacion Jimenez Diaz | Madrid | Spain | ||
| 13 | MD Anderson Cancer Center | Madrid | Spain | ||
| 14 | Hospital Universitario Virgen de la Victoria | Málaga | Spain | ||
| 15 | Clinica Universidad de Navarra | Pamplona | Spain |
Sponsors and Collaborators
- Genmab
- BioNTech SE
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GCT1046-04
- 2021-001928-17