E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable Metastatic Non-small Cell Lung Cancer |
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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 | 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 |
The primary objectives are:
For Phase 1 Combination Dose Selection: - To identify the RP2CD(s) of the amivantamab and capmatinib combination therapy in with NSCLC.
For Phase 2 Expansion: -To evaluate the antitumor effect of the amivantamab and capmatinib combination therapy in MET exon 14 skipping mutation and MET amplified NSCLC, when administered at the selected RP2CD(s)
Refer to Section 3 of Master protocol PLATFORMPANSC2001 for other primary objectives / endpoints.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
For Phase 1 Combination Dose Selection: - To further evaluate safety and tolerability of the amivantamab and capmatinib combination therapy
For Phase 2 Expansion (Cohorts 1A, 1B, and 1C): - To further assess the clinical benefit achieved by the amivantamab and capmatinib combination therapy - To assess Health-related Quality of Life (Cohort 1A)
Refer to Section 3 of Master protocol PLATFORMPANSC2001 for other secondary objectives / endpoints. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Previously diagnosed with histologically or cytologically confirmed unresectable Stage IV (metastatic) non-small cell lung cancer (NSCLC) (any histology) - May have: definitively, locally treated brain metastases that are clinically stable and asymptomatic for greater than (>) 2 weeks and who are off or receiving low-dose corticosteroid treatment (less than or equal to [<=]10 milligrams (mg) prednisone or equivalent) for at least 2 weeks prior to start of study treatment - May have a prior malignancy (other than the disease under study) the natural history or treatment of which is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s) - Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - A participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
Please refer to Master Protocol PLATFORMPANSC2001 and protocol ISA 61186372PANSC2001 for additional inclusion criteria |
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E.4 | Principal exclusion criteria |
- Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening - Participant has impairment of the gastrointestinal function that could affect absorption of capmatinib or is unable or unwilling to swallow tablets - Participant has symptomatic central nervous system (CNS) metastases which are neurologically unstable or have required increasing doses of steroids >10 mg prednisone or equivalent within the 2 weeks prior to study entry to manage CNS symptoms - Participant has uncontrolled tumor-related pain: Symptomatic lesions amenable to palliative radiotherapy (example, bone metastases, or metastases causing nerve impingement) should be treated more than 7 days prior to the administration of the first study treatment
Please refer to Master Protocol PLATFORMPANSC2001 and protocol ISA 61186372PANSC2001 for additional exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The Primary end points are:
For Phase 1 Combination Dose Selection: - Incidence and Severity of AEs, including Dose Limiting Toxicities (DLTs)
For Phase 2 Expansion: - Objective response rate (ORR) according to RECIST v1.1 by investigator review; confirmatory analysis may be performed using blinded independent central review (BICR)
Refer to Section 3 of Master protocol PLATFORMPANSC2001 for other primary endpoints. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The Secondary end points are:
For Phase 1 Combination Dose Selection: - Incidence and Severity of AEs and Clinical Laboratory Abnormalities
For Phase 2 Expansion (Cohorts 1A, 1B, and 1C): - Duration of response (DoR) confirmatory analysis may be performed using BICR - Disease control rate (DCR) - Progression free survival (PFS) according to RECIST v1.1 by investigator review - Overall Survival (OS) - Time to subsequent therapy (TTST) - EORTC-QLQ-C30 change from baseline - NSCLC-SAQ - EQ-5D-5L - PROMIS-PF
Refer to Section 3 of Master protocol PLATFORMPANSC2001 for other secondary endpoints. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Biomarkers and Immunogenicity Assessments |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Recommended Phase 2 combination Dose Study (RP2CD) |
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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 | Yes |
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 | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Brazil |
Canada |
China |
Japan |
Korea, Republic of |
United Kingdom |
United States |
France |
Germany |
Italy |
Poland |
Spain |
Türkiye |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 26 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 11 |