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

  • STATUS
    Recruiting
  • End date
    Jun 15, 2028
  • participants needed
    43
  • sponsor
    Criterium, Inc.
Updated on 4 October 2022
KRAS
metastasis
neutrophil count
brain metastases
lung carcinoma

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.

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.

Details
Condition Non Small Cell Lung Cancer
Treatment AMG 510, MVASI
Clinical Study IdentifierNCT05180422
SponsorCriterium, Inc.
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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
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)
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