E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant Solid Tumors - Non Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Locally advanced or metastatic non-small cell lung cancer in patients who failed a first line of treatment. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the anti-tumor activity of GEN1046 as monotherapy and in combination with pembrolizumab in subjects with relapsed/refractory metastatic NSCLC |
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E.2.2 | Secondary objectives of the trial |
• Evaluate time to onset and durability of the anti-tumor response of GEN1046 as monotherapy and in combination with pembrolizumab in subjects with relapsed/refractory metastatic NSCLC
• Evaluate the clinical benefit of GEN1046 as monotherapy and in combination with pembrolizumab
• Assess safety and tolerability of GEN1046 as monotherapy and in combination with pembrolizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 PDL1 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. |
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E.4 | Principal 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 anti-infective therapy that has been administered <2 weeks prior to first dose or any ongoing systemic inflammatory condition requiring further
diagnostic work-up or management during screening.
- 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by investigator |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
ORR is defined as the proportion of subjects with a confirmed response of partial response (PR)
or complete response (CR) according to RECIST v1.1 criteria. The minimum time from first infusion of trial drug required to qualify for an assessment of stable disease (SD) is 5 weeks, corresponding to the minimum planned time of the first imaging assessment.
Disease will be evaluated per RECIST v1.1. CT with contrast (preferred) or MRI will be obtained at baseline before the first dose and 6, 12, 18, and 24 weeks (±7 days) after the first dose of trial medication, and thereafter, every 9 weeks (±7 days). CT or MRI will continue to be obtained until disease progression, start of subsequent anti-cancer therapy, withdrawal of consent, or death, whichever occurs first. |
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E.5.2 | Secondary end point(s) |
• Duration of response (DOR) per RECIST v1.1
• Time to response (TTR) per RECIST v1.1
• Progression-free survival (PFS) per RECIST v1.1
• Overall survival (OS)
• Incidence and severity of AEs
• Incidence and severity of laboratory abnormalities |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- DOR: DOR is defined for responders as the time from initial onset of response to first progression event, defined as radiographic progression or death.
- TTR: Time to response (TTR) is defined as the time from first infusion of trial drug to onset of response.
- PFS: PFS is defined as the time from first infusion of trial drug to first progression event, defined as radiographic progression or death.
- OS: OS is defined as time from first infusion of trial drug to death due to any cause.
- Safety, including AEs, physical examinations, Eastern Cooperative Oncology Group (ECOG)performance status (PS), vital signs, electrocardiograms, and laboratory values, will be monitored throughout the trial. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Immunogenicity, Biomarker Analyses, Health-related Quality of life |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United Kingdom |
United States |
France |
Germany |
Italy |
Netherlands |
Poland |
Portugal |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial is considered completed when the last subject dies or withdraws from the trial. However, maximal trial duration is up to 3 years after the last subject’s first treatment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |