A clinical study of bemcentinib with standard of care chemoimmunotherapy in untreated advanced/metastatic non-small cell lung cancer patients with a mutation in the STK11 gene

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bergenbio ASA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Oct 2023 → 3 Apr 2025

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BerGenBio ASA

External identifiers

EU CT number

2024-511007-41-00

EudraCT number

2019-003806-28

ClinicalTrials.gov

NCT05469178

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Pharmacogenomic, Dose response, Safety, Pharmacokinetic, Therapy

Phase 1b:
To determine the safety and tolerability of the combination of bemcentinib with chemo-immunotherapy (CIT) to identify the recommended phase 2 dose (RP2D) when administered as first line (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.

Secondary objectives 1

1. 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.

Conditions and MedDRA coding

Untreated advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without/with a STK11 mutation.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 mutation, 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.

Exclusion criteria 5

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 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 Torsade de Point risk that need to be excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase 1b: The incidence of dose limiting toxicities (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: Objective response rate (ORR - complete response and partial response per RECIST 1.1) at 6 and 12 months.

Secondary endpoints 7

1. Phase 1b: - ORR (complete response and partial response per RECIST 1.1) Phase 2a: - The frequency and percentage of AEs; assessment of safety laboratory parameters, vital signs, and ECGs per CTCAE
2. Phase 1b: - Disease control rate (DCR) (complete response, partial response, and stable disease per RECIST 1.1) Phase 2a: - DCR (complete response, partial response, and stable disease)
3. Phase 1b: - Duration of response (DOR) Time of first response to progressive disease as assessed per RECIST 1.1) Phase 2a: - DOR
4. Phase 1b: - Overall survival Phase 2a: - Progression free survival (PFS)
5. Phase 2a: - Time to progression (TTP)
6. Phase 2a: - Overall survival
7. Phase 2a: - PK exposure (Cmax, AUC, and t½)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bergenbio ASA

Sponsor organisation

Bergenbio ASA

Address

Nygaardsgaten 114

City

Bergen

Postcode

5008

Country

Norway

Scientific contact point

Organisation

Bergenbio ASA

Contact name

Clinical Project Manager

Public contact point

Organisation

Bergenbio ASA

Contact name

Clinical Project Manager

Third parties 15

Locations

6 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 70 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications