E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Solid Tumor Malignancies |
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E.1.1.1 | Medical condition in easily understood language |
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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 | LLT |
E.1.2 | Classification code | 10065143 |
E.1.2 | Term | Malignant solid tumour |
E.1.2 | System Organ Class | 100000004864 |
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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 |
• To evaluate the antitumor activity of Sym015 when administered at the Q2W RP2D to patients in the following cohorts:
• Basket Cohort: MET-amplified, KRAS WT solid tumor malignancies without available therapeutic options
• NSCLC MET-Amplified Cohort: MET-amplified advanced NSCLC without available therapeutic options
• NSCLC METEx14Del Cohort: METEx14Del advanced NSCLC without available therapeutic options
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E.2.2 | Secondary objectives of the trial |
1. To further evaluate the safety and tolerability of Sym015 when administered at the Q2W RP2D
2. To further evaluate the PK profile of Sym015 when administered at the Q2W RP2D
3. To further evaluate the immunogenicity of Sym015 when administered at the Q2W RP2D
4. To further evaluate potential pharmacodynamic biomarkers of Sym015 action, and estimate, if feasible, the magnitude of biological activity when administered at the Q2W RP2D
5. Basket Cohort: To make a preliminary assessment of the antitumor activity of Sym015, and to evaluate all of the above secondary objectives, in a subset of approximately 6 patients with solid tumor malignancies administered Sym015 at the Q2W RP2D after
having received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main inclusion criteria all patients, Part 1 and Part 2:
• Male or female, at least 18 years of age at the time of informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Life expectancy >3 months assessed during Screening
• Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic, and that is refractory to standard therapy or for which no standard therapy is available (i.e. patients must have recurrent and/or progressive disease and be without other therapeutic options)
Additional main inclusion criteria applicable to Part 2 ONLY:
• Measurable disease according to RECIST v1.1 that has been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to Cycle 1/Day 1 (C1/D1)
Basket Cohort ONLY:
• Tumor documented to be KRAS WT by local assessment according to institutional standards.
• Confirmed MET-amplification
• No prior therapy with MET-targeting agents
NSLC MET-Amplified Cohort ONLY:
• Documented NSCLC meeting disease criteria as defined above
• Documented MET-amplification by either:
- Local assessment in a recent tumor biopsy
- Central confirmation in a newly performed pre-dosing tumor biopsy
• may have received prior therapy with MET-targeting and/or EGFR-targeting agents (antibodies or TKIs)
NSCLC METEx14Del Cohort ONLY:
• Documented NSCLC meeting disease criteria as defined above
• Documented METEx14Del (tumors need not be MET-amplified)
• May have received prior therapy with MET-targeting and/or EGFR-targeting agents (antibodies or TKIs) |
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E.4 | Principal exclusion criteria |
Main exclusion criteria all patients, Part 1 and Part 2:
• Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to C1/D1 except: nitrosoureas and mitomycin C within 6 weeks prior to C1/D1
• Immunosuppressive or systemic hormonal therapy (> 10 mg daily prednisone equivalent) within 2 weeks prior to C1/D1 (for exceptions,
see Protocol Section 7.5.2)
• Use of hematopoietic growth factors within 2 weeks prior to C1/D1
• Active second malignancy or history of another malignancy within the last 3 years, with specified allowed exceptions
• Central nervous system (CNS) malignancy including primary malignancies of the CNS, known untreated CNS or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS involvement for which treatment is required
• Inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy
• Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any prior surgical procedure
• Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 1 month prior to C1/D1, unless adequately treated and stable
• Active uncontrolled bleeding or a known bleeding diathesis
• Significant cardiovascular disease or condition
• Abnormal hematologic, renal or hepatic function
• Any of the following within 2 weeks prior to C1/D1:
o Any serious or uncontrolled infection
o Any infection requiring parenteral antibiotics
o Unexplained fever >38.0 °C
Part 2 – Basket Cohort ONLY :
• Prior therapy with MET-inhibiting agents
• Prior therapy with antibody to HGF |
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E.5 End points |
E.5.1 | Primary end point(s) |
Documented objective response (OR) (defined as partial response [PR] or complete response [CR]) in the Basket Cohort, assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At any time during trial participation by Investigator assessment |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
Denmark |
Korea, Republic of |
Spain |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |