Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
41
Countries
5
Sites
7
Non-small cell lung cancer (NSCLC)
To evaluate the tumor objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria in subjects who receive sotorasib at either 960mg daily (QD) or 240 mg QD whose tumors are programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) < 1% and /or harbor a serine /th…
Key facts
- Sponsor
- Amgen Inc.
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 23 Dec 2021 → 21 May 2026
- Decision date (initial)
- 2024-06-03
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Amgen Inc.
External identifiers
- EU CT number
- 2024-511189-36-00
- EudraCT number
- 2021-002638-18
- WHO UTN
- U1111-1305-1272
- ClinicalTrials.gov
- NCT04933695
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety, Pharmacokinetic
To evaluate the tumor objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria in subjects who receive sotorasib at either 960mg daily (QD) or 240 mg QD whose tumors are programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) < 1% and /or harbor a serine /threonine kinase 11 (STK11) co-mutation, in a subgroup of subjects with PD-L1 <1% and in a sub-group of subjects with STK11 co-mutation
Secondary objectives 3
- To evaluate other measures of efficacy
- To evaluate the safety and tolerability of Sotorasib
- Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral tablet formulation
Conditions and MedDRA coding
Non-small cell lung cancer (NSCLC)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10029522 | Non-small cell lung cancer stage IV | 100000004864 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Randomized study. Treatment phase. Open-label, multicenter phase 2 study to explore the anti-tumor effect of sotorasib monotherapy in subjects with metastatic NSCLC with KRAS p.G12C mutation in need of this first line treatment. Subjects will be ranzomized for treatment with sotorasib at 960 mg QD or 240 mg QD.
|
Not Applicable | None | 960 mg treatment arm: Subjects will receive sotorasib 960 mg oral daily 240 mg treatment arm: Subjects will receive sotorasib 240 mg oral daily |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Adult 18 years or older with NSCLC
- Untreated Stage IV metastatic disease. Participants who received adjubant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed greter than 12 months prior to the deveolpment of metastatic disease
- Pathologically documented metastatic NSCLC with KRAS G12C mutation (local confirmation)
- Programmed death-ligand 1 (PD0L1) TPS Score less than 1 percent and or serine threonine kinase 11 (STK11) co-mutation (local confirmation)
- Eastern Cooperatiove Oncology Group (ECOG) score of 0 or 1
- No active brain metastases
- Measurable disease per investigator interpretation using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
Exclusion criteria 7
- Mixed small-cell lung cancer and NSCLC histology.
- Active brain metastases from non-brain tumors
- Use of proton-pump inhibitors (PPIs), histamine (H2) receptor antagonistes (H2RA), strong inducers of cytochrome P450 (CYP) 3A4 (CYP3A4) or known CYP3A4 sensitive substrates or P-gp substrates
- Therapeutic or palliative radiation therapy within 2 weeks of study day 1
- Unable to take oral medication
- Unable to receive both iodinated contrast for computed tomorgraphy (CT) scans and gadolinium contrast for magnetic resonance imagine (MRI) scans
- Myocardial infarction within 6 months of study day 1
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Objective response (OR) (OR = complete response [CR] + partial response [PR]), measured by computed tomography (CT) or magnetic resonance imaging (MRI) and assessed per RECIST 1.1 per Blinded Independent Central Review (BICR)
Secondary endpoints 7
- Disease control (CR + PR + stable disease [SD])
- Duration of response (DOR)
- Time to response (TTR)
- Progression-free survival (PFS)
- Overall survival (OS)
- Treatment-emergent adverse events, treatment-related adverse events, and changes in vital signs, electrocardiogram [ECGs], and clinical laboratory tests.
- PK parameters of sotorasib including, but not limited to, maximum plasma concentration (Cmax), time to achieve Cmax (tmax), and area under the plasma concentration-time curve (AUC)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB197397 · Substance
- Active substance
- Sotorasib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 960 mg milligram(s)
- Max total dose
- 698880 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Please refer to the sotorasib IMPD-Q enclosed with the application
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Amgen Inc.
- Sponsor organisation
- Amgen Inc.
- Address
- 1 Amgen Center Drive
- City
- Thousand Oaks
- Postcode
- 91320-1730
- Country
- United States
Scientific contact point
- Organisation
- Amgen Inc.
- Contact name
- Medical Information
Public contact point
- Organisation
- Amgen Inc.
- Contact name
- Medical Information
Third parties 4
| Organisation | City, country | Duties |
|---|---|---|
| Almac Clinical Technologies LLC ORG-100043036
|
Souderton, United States | Interactive response technologies (IRT) |
| Worldcare Clinical LLC ORG-100047766
|
Waltham, United States | Other |
| Eresearchtechnology Inc. ORG-100013039
|
Philadelphia, United States | Other |
| Labcorp Central Laboratory Services LP ORG-100032236
|
Indianapolis, United States | Laboratory analysis |
Locations
5 EU/EEA countries · 7 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ended | 4 | 1 |
| France | Ended | 1 | 1 |
| Italy | Ended | 12 | 2 |
| Spain | Ended | 4 | 1 |
| Sweden | Ended | 2 | 2 |
| Rest of world
United States, Turkey
|
— | 18 | — |
Investigational sites
Centre Hospitalier Universitaire De Bordeaux
Service des maladies respiratoires, Avenue De Magellan, 33600, Pessac
Fondazione IRCCS San Gerardo Dei Tintori
Unita Operativa di Oncologia Medica, Via Giovanni Battista Pergolesi 33, 20900, Monza
I.F.O. Istituti Fisioterapici Ospitalieri
Oncologia Medica 2, Via Elio Chianesi N 53, 00144, Rome
Hospital Universitario Y Politecnico La Fe
Servicio de Oncologia, Avenida De Fernando Abril Martorell 106, 46026, Valencia
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2022-01-19 | 2025-07-15 | 2022-05-19 | 2022-08-05 | |
| France | 2022-01-28 | 2025-07-31 | 2022-07-20 | 2022-08-05 | |
| Italy | 2021-12-23 | 2025-07-30 | 2022-02-09 | 2022-08-05 | |
| Spain | 2022-01-28 | 2025-07-18 | 2022-03-30 | 2022-08-05 | |
| Sweden | 2022-01-10 | 2025-08-22 | 2022-05-03 | 2022-08-05 |
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
| Title | Submission date | Status | Type |
|---|---|---|---|
| Technical Results Summary_Final Analysis SUM-135222
|
2026-05-21T13:49:47 | Submitted | Summary of Results |
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_ENG_ 2024-511189-36_20190288_For Publication | 5 |
| Recruitment arrangements (for publication) | K1_Recruitement arrangements_Dummy document_For Publication | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_ recruitment procedure_For Publication | 1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Pharmacogenetic_For Publication | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_FOR PUBBLICATION | 5.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_For Publication | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Privacy_FOR PUBBLICATION | 1.0 |
| Summary of results (for publication) | sotorasib_20190288_Technical Results Summary_Final Analysis | 1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-19 | Belgium | Acceptable 2024-05-30
|
2024-05-31 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-09-25 | Belgium | Acceptable 2024-05-30
|
2024-09-25 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-05-13 | Acceptable 2024-05-30
|
2025-05-13 | |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-07-21 | Belgium | Acceptable 2024-05-30
|
2025-07-21 |