| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| untreated advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without/with a STK11 mutation |
|
| E.1.1.1 | Medical condition in easily understood language |
| a specific type of untreated advanced or metastatic lung cancer called non-squamous non-small cell lung cancer (NSCLC) which consists of an abnormal growth of cells in the lining of the lungs. |
|
| 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 | 27.1 |
| 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) |
|
| 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 |
Phase 1b:
To determine the safety and tolerability of the combination of bemcentinib with CIT to identify the recommended phase 2 dose (RP2D) when administered as 1L treatment in subjects with advanced (Stage IIIb/IIIC) or metastatic (Stage IV) non-squamous NSCLC with no actionable mutations.
Phase 2a:
To determine the anti-tumor activity of the combination of bemcentinib with CIT when administered as 1L treatment in subjects with advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC with STK11 mutation and no actionable mutations. |
|
| E.2.2 | Secondary objectives of the trial |
Phase 1b:
To assess the anti-tumor activity of the combination of bemcentinib with CIT when administered as 1L treatment in subjects with locally advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC with no actionable mutations
Phase 2a:
To further assess the anti-tumor activity as well as the safety and pharmacokinetic profile of the combination bemcentinib with CIT when administered as 1L treatment in subjects with advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC with STK11 mutation and no actionable mutations. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. The subject (or legally acceptable representative, if applicable) must provide written informed consent for the study prior to any screening procedures.
2. Be ≥ 18 years of age on the day of signing the informed consent.
3. Have a histologically- or cytologically confirmed diagnosis of advanced (Stage IIIb/IIIc) or metastatic (Stage IV) (AJCC Edition 8) non-squamous NSCLC not amenable to curative therapy, irrespective of PD-L1 status and without actionable mutations (Phase 1b).
4. Have a histologically- or cytologically confirmed diagnosis of advanced (Stage IIIb/IIIC) or metastatic (Stage IV) (AJCC, Edition 8) non-squamous NSCLC with STK11m, not amenable to curative therapy, irrespective of PD-L1 status and without actionable mutations (Phase 2a).
5. Participants who received prior neo-adjuvant or adjuvant/consolidation treatment (radiotherapy, chemotherapy, immunotherapy) or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months since the last dose of chemotherapy, immunotherapy and/or radiotherapy before enrollment
6. Have measurable disease per RECIST 1.1 as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
The exhaustive list of the inclusion criteria is available in the protocol. |
|
| E.4 | Principal exclusion criteria |
1. Has received any prior chemotherapy or biological therapy for advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC.
2. Has any actionable mutation that is considered targetable with first-line treatment.
3. Has a known history of prior malignancy except if the subject has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy.
4. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate,
provided they are radiologically stable, i.e. without evidence of progression for at least 2 weeks and have no evidence of new or enlarging brain metastases and are off steroids 7 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study medication. Subjects with asymptomatic brain metastases (i.e. no neurological symptoms, no requirements for corticosteroids, and no lesion >1.5cm) may participate but will require regular imaging of the brain as a site of disease. Subjects who have experienced an acute neurological event (e.g. intracranial or subarachnoid haemorrhage, stroke, intracranial trauma) within 6 months prior to study enrolment will be excluded.
5. History of the following cardiac conditions:
a. Congestive cardiac failure of >Grade II severity according to the New York Heart Association (NYHA) or resistant or inadequately treated heart failure.
b. Ischemic cardiac event including myocardial infarction prior to first dose or hospitalization for unstable angina within 3 months prior to first dose.
c. Abnormal left ventricular ejection fraction on echocardiography or multigated acquisition scan (MUGA) (less than the lower limit of normal for a subject of
that age at the treating institution or <45%, whichever is lower), or history of cardiomyopathy or left ventricular hypertrophy.
d. Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension (i.e. sustained systolic blood pressure (BP) >160 mmHg or diastolic BP >90 mmHg), or need to change medication due to lack of disease control within 12 weeks prior to the provision of consent.
e. History or presence of sustained bradycardia (≤55 bpm) or history of symptomatic bradycardia, left bundle branch block, cardiac pacemaker or significant arrhythmias or any conduction disorder within 6 months prior to dosing as defined by the need for treatment.
f. Family history of long QTc syndrome or ventricular arrhythmias; personal history of long QTc syndrome or previous drug induced QTc prolongation of at least Grade 3 (QTc >500ms).
g. Presence of any other risk factors that increase the risk of QTc prolongation, specifically, hypokalemia or hypomagnesemia (if corrected the subject may be enrolled) or inadequately treated hypothyroidism (defined as thyroid stimulating hormone (TSH) below the expected range).
h. Current treatment with any agent known to cause QT prolongation and have a risk for Torsades de pointes (TdP), which cannot be discontinued at least 5 and
½ half-lives or 2 weeks prior to the first dose of study treatment, with the exception of antiemetics (e.g. ondansetron) which may be required. Please see
https://crediblemeds.org for a list of medications with known TdP risk that need to be excluded.
The exhaustive list of the exclusion criteria is available in the protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase 1b:
The incidence of DLTs during a 21-day assessment period in treatment cycle 1 (i.e., the first 21 days from Cycle 1 Day 1 [C1D1] for each subject)
Phase 2a:
ORR (complete response and partial response per RECIST 1.1) (Eisenhauer et al., 2009) at 6 and 12 months. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Refer to protocol endpoint timepoints |
|
| E.5.2 | Secondary end point(s) |
Phase 1b:
ORR (complete response and partial response
per RECIST 1.1)
Disease control rate (DCR) (complete response, partial response, and stable disease per RECIST 1.1)
Duration of response (DOR) Time of first response to progressive disease as assessed per RECIST 1.1)
Overall survival
Phase 2a:
The frequency and percentage of AEs and SAEs; assessment of safety laboratory parameters, vital signs, and ECGs per CTCAE
DCR (complete response, partial response, and stable disease)
DOR
Progression free survival (PFS)
Time to progression (TTP)
Overall survival
PK exposure (Cmax, AUC, and t½) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Refer to protocol endpoint timepoints |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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 |
| dose finding/escalation study |
|
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| 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 States |
| France |
| Greece |
| Hungary |
| Italy |
| Poland |
| Spain |
|
| 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
|
| Last Subject Last Visit (LPLV) including the survival follow-up phase |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 2 |
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