A performance evaluation study for the testing of DNA extracted from either tumor tissue biopsy samples or plasma, using the therascreen® EGFR Plus RGQ PCR Kit, from subjects with Non-Small Cell Lung Cancer, being screened for inclusion in Taiho Oncology, Inc*s Clinical Trial (Protocol No. 10073010).

Conditions: Lung Cancer
Non Small Cell Lung Cancer
10038666

Registration Number: NL-OMON56744

Lead Sponsor: QIAGE

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

1. Provide written informed consent
2. >=18 years of age (or meets the country*s regulatory definition for legal
adult age,
whichever is greater)
3. Histologically or cytologically confirmed, locally advanced, non-resectable
or metastatic
NSCLC
4. Has received the following prior treatment and no more than 2 lines of prior
cytotoxic
chemotherapy for locally advanced or metastatic disease setting:
a. Part A1 (Phase 1 Dose Escalation): Standard of care (SOC) that is
available to the
patient, unless contraindicated or intolerable to the patient
b. Part A2: Progression on third-generation EGFR TKI (eg, osimertinib,
lazertinib) and having received or not eligible for platinum-based
chemotherapies or other
targeted approved therapies in case of off-target alterations.
c. Parts B, and C: Progression on third-generation EGFR TKI (eg,
osimertinib,
lazertinib)
5. Has the following EGFRmt status as determined by a CLIA certified (US),
locally
certified (outside of the US), or the study central laboratory based on tumor
tissue or
plasma cfDNA:
a. Part A1 (Phase 1 Dose Escalation): Any EGFRmt
b. Parts A2, B, and C: Any sensitizing EGFRmt and a confirmed C797S EGFRmt
(Note: no T790M EGFRmt required)
6. Has tumor tissue available collected after progression on the most recent
systemic EGFR
TKI treatment in a quantity sufficient to allow for analysis of EGFRmt status
by the
Sponsor*s central laboratory (optional for Part A1 only). Please refer to the
Laboratory
Manual for details.
7. Has measurable disease per RECIST v1.1 (optional for patients in Part A1)
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
9. Adequate organ function as defined by the following criteria:
a. Absolute neutrophil count (ANC) >= 1.5 × 109/L
b. Platelet count >= 100,000/mm3 (>= 100 × 109/L); last transfusion of blood
products
must be >=2 weeks prior to start of study treatment.
c. Hemoglobin >= 9.0 g/dL
d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=
3.0 × upper
limit of normal (ULN); if liver function abnormalities are due to
underlying liver
metastasis, AST and ALT <= 5.0 × ULN
e. Total bilirubin <= 1.5 × ULN, or <= 3.0 × ULN for patients with Gilbert*s
syndrome
f. Creatinine clearance (CrCl) (calculated or measured value): >=50 mL/min.
For
calculated CrCl, use the Cockcroft-Gault formula
g. Potassium blood levels >=3.0 mmol/L
10. Women of child-bearing potential (WOCBP) must have a negative serum
pregnancy test
prior to administration of the first dose of study treatment. Female patients
are not
considered to be of child-bearing potential if they are post-menopausal (no
menses for
12 months without an alternative medical cause) or permanently sterile
(hysterectomy,
bilateral salpingectomy, or bilateral oophorectomy).
11. Both males and females of reproductive potential must agree to use highly
effective birth
control throughout the study and at least for:
* 6 months after the last dose of study treatment for females
* 3 months after the last dose of study treatment for males
or longer, based on local requirements

In addition to the above, patients in France must meet the following criterion:

12. Affiliated with a social security system or be a beneficiary of an <br

Exclusion Criteria

1.Currently receiving an investigational drug in a clinical trial or
participating in any other
type of medical research judged not to be scientifically or medically
compatible with this
study
2. Has received prior treatment with any of the following within the specific
time frame
prior to the first dose of study treatment:
a. Major surgery/surgical therapy for any cause within 4 weeks; the patient
must have
recovered adequately from the toxicity and/or complications of the
intervention prior
to starting study treatment
b. Chemotherapy, biologic therapy, targeted therapy, immunotherapy, or
investigational
agents within 5 half-lives or within 4 weeks (whichever is shorter)
prior to the first
dose of study treatment. Patient must have recovered from toxicities of
the prior
therapy based on the Investigator*s judgement prior to starting study
treatment
c. No prior treatment with:
(i) Part A1 (Phase 1 Dose Escalation): Systemic immunotherapy (eg, PD-
1/PD-L1 antibody)
(ii) Parts A2, B, and C: Any EGFR C797S mutation-targeting agent (eg,
BLU-945)
d. Radiotherapy prior to the start of study treatment within:
(i). 2 weeks for radiation therapy of non-thoracic regions (7 days
for palliative
radiation of single lesions)
(ii). 3 months for radiation therapy including thoracic region.
Patients must have recovered from all radiation-related toxicities, not
require
corticosteroids, and not have had radiation pneumonitis.
3. Have any unresolved clinically relevant toxicity of Grade >= 2 from previous
anti-cancer
treatment, except for alopecia, skin pigmentation, and Grade 2, prior
platinum-therapy
related neuropathy. Patients with chronic, but stable Grade 2 toxicities may be
allowed to
enroll if the Investigator and Sponsor agree.
4. Any strong and moderate inhibitors/inducers of cytochrome P450 (CYP) 3A two
weeks
prior to start of therapy. If a patient is receiving strong inhibitors/inducers
of CYP3A , these medications and substances must be discontinued >=2 weeks prior
to the first dose of study treatment.
5. Has the following CNS metastases disease status:
a. Part A1 (Phase 1 Dose Escalation): Known untreated central nervous
system (CNS)
metastases, or history of uncontrolled seizures, or leptomeningeal disease.
Patients
with treated brain metastases are eligible if there is no evidence of
progression for at
least 4 weeks after CNS-directed treatment, as ascertained by clinical
examination
and brain imaging (MRI or CT scan) during the screening period, and they
are on a
stable or decreasing dose of corticosteroids for at least 2 weeks prior to
the first dose
of study treatment.
b. Part A2, B, and C: Spinal cord compression, symptomatic and unstable CNS
metastases, requiring steroids over the last 4 weeks prior to enrollment
(asymptomatic and symptomatic brain metastases stable for at least 4 weeks
and off
steroids are allowed). Patients with leptomeningeal disease are allowed if
it is determined that
immediate CNS treatment is unlikely to be required.
6. Impaired cardiac function or clinically significant cardiac disease,
including any of the
following:
a. Baseline QT interval > 470 msec corrected for heart rate using
Fridericia*s formula
(QTcF, verified on repeat measure

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint of the Phase 1 Dose Escalation part of this study is to<br /><br>identify the RP2D based on safety and preliminary antitumor activity observed<br /><br>as standard for Phase 1 first in human studies.<br /><br><br /><br>The primary endpoint of the Phase 1 Dose Expansion and the Phase 2 part is<br /><br>Overall response rate (ORR) assessed by Independent Central Review (ICR)<br /><br>according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. ORR is<br /><br>a clinically meaningful and accepted endpoint by regulatory agencies for<br /><br>studies in later-line EGFRmt NSCLC patients. ORR will be assessed by ICR to<br /><br>avoid any potential Investigator bias and to increase the validity of the ORR<br /><br>results observed.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>As a key secondary objective, this study will include Duration of response<br /><br>(DoR) as assessed by ICR to evaluate the durability of responses. Durability of<br /><br>responses are considered a key factor to determine whether an observed ORR is<br /><br>clinically meaningful.</p><br>