Non Small Cell Lung CancerPhase 1/2NCT05180422
A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis
A Phase 1/2 study testing AMG 510 and MVASI in people with Non Small Cell Lung Cancer, run by Criterium, Inc. at 1 site in United States.
Trial summary
This is a multicenter, non-randomized, open-label, phase I/II study to evaluate the safety and tolerability of AMG 510 plus MVASI in subjects with advanced KRAS p.G12C mutant non-small cell lung cancer (NSCLC) with small, untreated brain metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- AMG 510 and MVASI
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2022to 31 Jan 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- Signed and dated written informed consent.
- Male or female ≥ 18 years of age at the time of informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- As estimated by study physician, life expectancy ≥ 12 weeks.
- Histologically proven, locally advanced, recurrent or metastatic KRAS G12C mutant non-small cell lung cancer (NSCLC), with pathological documentation of KRAS p.G12C mutation identified through DNA sequencing either in tumor tissue or blood circulating tumor DNA.
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- At least one untreated brain metastasis ≥ 5mm in diameter in any line of treatment:
- Subjects with largest measurable intracranial lesion ≥5 mm but <10 mm may be allowed to enroll upon agreement with investigator (for patients with target lesions of ≥ 5mm but <10 mm, 1.5 mm slice thickness brain MRI is required).
- "Untreated" refers to the lesion not being previously treated with stereotactic radiosurgery (SRS).
- Prior treatment with whole brain radiation therapy or local surgery is permissible provided unequivocal progression in the lesion has since occurred and completion 14 days prior to study enrollment.
- For at least 7 days prior to first dose of AMG 510 and MVASI in this study: Patient must be asymptomatic from CNS metastases and on a stable dose of corticosteroids.
- Able to take oral medications and willing to record daily adherence to investigational product.
- As assessed by electrocardiogram (ECG) completed ≤ 14 days before initiation of protocol treatment, the corrected QT interval (QTc) will be calculated by Fridericia's method (QTcF) - see Section 7.12. Eligible candidates (male or female) must have the following QTcF value on baseline ECG:
- QTcF ≤ 470 ms.
- The average QTcF value from three (3) separate ECG tracings, each performed on the same day (ideally at least 5 minutes apart), will serve as the baseline QTcF value used to meet eligibility.
- Adequate organ and bone marrow function resulted ≤ 14 days prior to first dose of protocol-indicated treatment:
- Prothrombin time (PT) and partial thromboplastin time (PTT) < 1.5x institutional upper limit of normal (ULN).
- Absolute neutrophil count (ANC) > 1500/µL.
- Hemoglobin ≥ 9 g/dL.
- Platelets ≥ 75,000/µL.
- Total bilirubin ≤ 1.5x ULN; or
- < 2x ULN in subjects with documented Gilbert's syndrome; or
- < 3x ULN in subjects for whom the indirect bilirubin level suggests an extrahepatic source of total bilirubin elevation).
- AST (SGOT) and ALT (SGPT) ≤ 2.5x ULN; or
- ≤ 5x ULN if liver metastases are present.
- Serum creatinine ≤ 1.5mg/dL.
- Women must not be breastfeeding and further agree to not breastfeed during study treatment; and for at least 1 week (7 days) after patient's final dose of AMG 510, and for at least 6 months (183 days) after patient's final dose of MVASI.
- A woman of childbearing potential (WOCBP) - see Appendix 3 for definition of WOCBP - must have a negative serum or urine β-hCG pregnancy test (or in cases of β-hCG tumor production, may be confirmed not pregnant by uterine ultrasound during screening) within 14 days prior to receiving first dose of protocol-indicated treatment to be eligible, and must agree to follow instructions for using acceptable contraception (Appendix 3) from the time of signing consent, and until at least 6 months (183 days) after her final dose of AMG 510 and MVASI.
- A man able to father children (see Appendix 3 for definition) who is sexually active with a WOCBP must agree to follow instructions for using acceptable contraception (Appendix 3), from the time of signing consent, and until at least 6 months (183 days) after his final dose of AMG 510 and MVASI.
Who cannot join
- Patients meeting any of the following criteria will not be permitted to enter the trial:
- Other coexisting malignancies or malignancies diagnosed within the previous 2 years are not eligible.
- Exceptions to this include non-melanoma skin cancer, cervical cancer in-situ, well-differentiated thyroid cancer or prostate cancer.
- Other cancers that per assessment of the principal investigator are not prognosis-limiting can be allowed after review by the principal investigator. If there is no evidence of disease for at least 3 years prior to initiating treatment in this study, patients may be eligible.
- Prior receipt of AMG-510, other KRAS G12C inhibitors, or VEGF inhibitors for the treatment of non-small cell lung cancer.
- Myocardial infarction within 6 months of study Day 1, symptomatic congestive heart failure equivalent to New York Heart Association > Class II (see Appendix 2) or unstable (requiring hospitalization or heart catheterization) angina currently.
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- Patient on full dose, therapeutic anticoagulation for thromboembolic event, arrhythmia, or prothesis with coumadin.
- Evidence of clinically significant hemorrhage (per study physician) in untreated CNS lesion(s) on screening MRI.
- Major surgery within 28 days of enrollment or presence of a non-healing wound.
- Proteinuria of greater than 1 gram per 24 hours.
- Recent history of moderate or severe hemoptysis within 7 days (greater than 20mL of pure blood within 24 hours).
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
Official title: A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis.
This is a multicenter, non-randomized, open-label, phase I/II study to evaluate the safety and tolerability of AMG 510 plus MVASI in subjects with advanced KRAS p.G12C mutant non-small cell lung cancer (NSCLC) with small, untreated brain metastases.
Read the detailed description
Each patient is scheduled to receive AMG 510 (KRASG12C inhibitor) in combination with MVASI (vascular endothelial growth factor [VEGF] inhibitor; bevacizumab biosimilar); both drugs will be provided by the study:
AMG 510:
Continuous once daily (QD) oral dosing (Days 1-21 each cycle) with or without food.
MVASI:
Intravenous (i.v.) infusion every 21 days (i.e. Day 1 of each 21-day cycle).
The study will be conducted in 2 parts. The dose expansion part of the study (Part 2) can open once the maximum tolerated dose (MTD) and/or a biologically active dose (e.g. recommended phase 2 dose [RP2D]) using a 3+3 study design has been determined in Part 1.
CNS response will be assessed using RANO-BM criteria, and non-CNS objective response will be based on Solid Tumor Response Criteria [RECIST v1.1] assessment of overall tumor burden at baseline versus that detected on subsequent CT/MRI re-scans. This includes a brain MRI on C2D1 (21 days) and a CT chest/abdomen/pelvis (C/A/P) at 6 weeks, then brain MRI at 15 weeks and CT C/A/P imaging at 12-16 weeks, and then every 4 cycles (every 12 weeks) while on study. It is intended that patients will be treated until disease progression or intolerable toxicity. Patients will be followed for survival for up to 18 months after ending study treatment.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- AMG 510, MVASI
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 510Drug
Continuous once daily (QD) oral dosing (Days 1-21 each cycle) with or without food.
MVASIDrug
Intravenous (i.v.) infusion every 21 days (i.e. Day 1 of each 21-day cycle).
| Study group | Role | What they receive |
|---|---|---|
| Dose Expansion | Experimental | AMG 510/MVASI Receives: Drug: AMG 510; Drug: MVASI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Exploration
To determine the feasibility and safety of AMG 510 in combination with MVASI for the treatment of patients with KRAS G12C mutant NSCLC with asymptomatic, untreated brain metastases.
For patients enrolled in the dose exploration part of the study (anticipated to be the initial 9-18 patients participating in the study), whose participation will establish the recommended phase 2 dose (RP2D), dedicated surveillance and expedited reporting of Dose Limiting Toxicity (DLT) required for 21 days after initiating protocol-indicated treatment. Satisfactory completion of the physical exam and safety labs is required to help detect evidence of past or present DLT as having occurred during the first 21 days of protocol-indicated treatment.
Measured: 21 days
Dose Expansion
To determine the CNS objective response and rate of salvage radiation to the CNS 18 weeks after therapy initiation.
The CNS objective response rate using Rando-BM will be evaluated at 18 weeks. Whether or not the patient requires salvage radiation therapy will be evaluated at 18 weeks
Measured: 18 weeks
Dose Exploration
Safety and tolerability (phase I component).
Dedicated surveillance and expedited reporting of Dose Limiting Toxicity (DLT) is required for 21 days after initiating protocol-indicated treatment A minimum of 6 patients will be treated at the Maximum tolerated dose on the phase I portion of the study in order to obtain sufficient toxicity data prior to proceeding to the phase II evaluation of this regimen
Measured: 21 days
Dose Expansion
CNS objective response, assessed using RANO-BM.
Measured: 18 weeks
Dose Expansion
Initiation of salvage radiation therapy to the CNS at 18 weeks (phase II component).
Measured: 18 weeks
Secondary outcomes (4)
Dose Expansion
To evaluate systemic disease control by progression free survival and overall survival.
Measured: 18.5 months
Dose Expansion
Non-CNS overall response (ORR), assessed using RECIST v1.1.
Measured: 18 weeks
Dose Expansion
Non-CNS progression-free survival (PFS).
Measured: 18.5 months
Dose Expansion
Overall Survival (OS).
Measured: 18.5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2022
- Study start15 Jun 2022
- Primary completion31 Jan 2023
- Study completion31 Jan 2023
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Criterium, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- Wade Iams, MD, MSCI, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05180422
- Sponsor's protocol ID
- 02AT21-KRAS
- Status last verified
- Oct 2023
- First submitted
- 6 Dec 2021
- Last updated
- 18 Oct 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis.
- ClinicalTrials.gov ID
- NCT05180422
- Acronym / sponsor ID
- 02AT21-KRAS
- Conditions
- Non Small Cell Lung Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Criterium, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Amgen
- Study start
- 15 Jun 2022 (actual)
- Primary completion
- 31 Jan 2023 (actual)
- Study completion
- 31 Jan 2023 (actual)
- First posted
- 6 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, non-randomized, open-label, phase I/II study to evaluate the safety and tolerability of AMG 510 plus MVASI in subjects with advanced KRAS p.G12C mutant non-small cell lung cancer (NSCLC) with small, untreated brain metastases.
Detailed description
Each patient is scheduled to receive AMG 510 (KRASG12C inhibitor) in combination with MVASI (vascular endothelial growth factor [VEGF] inhibitor; bevacizumab biosimilar); both drugs will be provided by the study:
AMG 510:
Continuous once daily (QD) oral dosing (Days 1-21 each cycle) with or without food.
MVASI:
Intravenous (i.v.) infusion every 21 days (i.e. Day 1 of each 21-day cycle).
The study will be conducted in 2 parts. The dose expansion part of the study (Part 2) can open once the maximum tolerated dose (MTD) and/or a biologically active dose (e.g. recommended phase 2 dose [RP2D]) using a 3+3 study design has been determined in Part 1.
CNS response will be assessed using RANO-BM criteria, and non-CNS objective response will be based on Solid Tumor Response Criteria [RECIST v1.1] assessment of overall tumor burden at baseline versus that detected on subsequent CT/MRI re-scans. This includes a brain MRI on C2D1 (21 days) and a CT chest/abdomen/pelvis (C/A/P) at 6 weeks, then brain MRI at 15 weeks and CT C/A/P imaging at 12-16 weeks, and then every 4 cycles (every 12 weeks) while on study. It is intended that patients will be treated until disease progression or intolerable toxicity. Patients will be followed for survival for up to 18 months after ending study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Expansion | Experimental | Drug: AMG 510, Drug: MVASIAMG 510/MVASI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- Signed and dated written informed consent.
- Male or female ≥ 18 years of age at the time of informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- As estimated by study physician, life expectancy ≥ 12 weeks.
Key exclusion criteria (11 listed)
- Other coexisting malignancies or malignancies diagnosed within the previous 2 years are not eligible.
- Prior receipt of AMG-510, other KRAS G12C inhibitors, or VEGF inhibitors for the treatment of non-small cell lung cancer.
- Myocardial infarction within 6 months of study Day 1, symptomatic congestive heart failure equivalent to New York Heart Association > Class II (see Appendix 2) or unstable (requiring hospitalization or heart catheterization) angina currently.
- Patient on full dose, therapeutic anticoagulation for thromboembolic event, arrhythmia, or prothesis with coumadin.
- Evidence of clinically significant hemorrhage (per study physician) in untreated CNS lesion(s) on screening MRI.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 510Continuous once daily (QD) oral dosing (Days 1-21 each cycle) with or without food. | Drug | Dose Expansion |
| MVASIIntravenous (i.v.) infusion every 21 days (i.e. Day 1 of each 21-day cycle). | Drug | Dose Expansion |
Primary outcome
Dose Exploration
Time frame: 21 days
To determine the feasibility and safety of AMG 510 in combination with MVASI for the treatment of patients with KRAS G12C mutant NSCLC with asymptomatic, untreated brain metastases. For patients enrolled in the dose exploration part of the study (anticipated to be the initial 9-18 patients participating in the study), whose participation will establish the recommended phase 2 dose (RP2D), dedicated surveillance and expedited reporting of Dose Limiting Toxicity (DLT) required for 21 days after initiating protocol-indicated treatment. Satisfactory completion of the physical exam and safety labs is required to help detect evidence of past or present DLT as having occurred during the first 21 days of protocol-indicated treatment.
Dose Expansion
Time frame: 18 weeks
To determine the CNS objective response and rate of salvage radiation to the CNS 18 weeks after therapy initiation. The CNS objective response rate using Rando-BM will be evaluated at 18 weeks. Whether or not the patient requires salvage radiation therapy will be evaluated at 18 weeks
Dose Exploration
Time frame: 21 days
Safety and tolerability (phase I component). Dedicated surveillance and expedited reporting of Dose Limiting Toxicity (DLT) is required for 21 days after initiating protocol-indicated treatment A minimum of 6 patients will be treated at the Maximum tolerated dose on the phase I portion of the study in order to obtain sufficient toxicity data prior to proceeding to the phase II evaluation of this regimen
Dose Expansion
Time frame: 18 weeks
CNS objective response, assessed using RANO-BM.
Dose Expansion
Time frame: 18 weeks
Initiation of salvage radiation therapy to the CNS at 18 weeks (phase II component).
4 secondary outcomes
Dose Expansion
Time frame: 18.5 months
Dose Expansion
Time frame: 18 weeks
Dose Expansion
Time frame: 18.5 months
Dose Expansion
Time frame: 18.5 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wade Iams, MD, MSCI principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AMG 510 and MVASI in people with Non Small Cell Lung Cancer, run by Criterium, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Exploration (time frame: 21 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2023.