Inclusion Criteria:
- Provision of informed consent prior to any study specific procedures
- Histologic or cytological diagnosis of Squamous Cell Lung Cancer (SQCLC) with
advanced/metastatic stage, with no known curative treatment options. Prior
platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation therapy given
for locally advanced disease is considered first line therapy only if recurrent (local
or metastatic) disease developed within 6 months of completing therapy. Potential
participants with recurrent disease > 6 months will be eligible.
- Female or male aged >/= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0/1
- Prior chemotherapy in the adjuvant setting is allowed
- Prior radiotherapy is allowed
- Any prior palliative radiation must have been completed at least 7 days prior to the
start of the studies drugs and participants must have been recovered from any acute
adverse effects prior to the start of the study treatment
- Prior Immunotherapy with PD1i, PDL1i, anti-CTLA -4 or vaccines is allowed
- Must have normal organ and marrow function
- Have archival tissue available or undergo a fresh biopsy where clinically feasible
after discussion with the sponsor
- Women of childbearing potential and men must agree to use adequate contraception prior
to study entry and for the duration of study participation and women who are breast
feeding are excluded from the study. Both women and men should be fully informed of
the lack of reproductive toxicity testing, and women must have a negative pregnancy
test prior to enrollment.
Exclusion Criteria:
- Progressive, symptomatic untreated brain metastases
- Pregnancy or breast feeding
- A serious uncontrolled medical disorder or active infection that in the investigator's
opinion would impair the participant's ability to receive study treatment
- Prior use of platinum or paclitaxel for stage IV Non-small Cell Lung Cancer (NSCLC) or
concurrent use of other anticancer approved or investigational agents
- Use of anti-cancer treatment drug ?21 days or 5 half-lives (whichever is shorter)
prior to the first dose of AZD1775. For drugs for which 5 half-lives is <21 days, a
minimum of 10 days between termination of the prior treatment and administration of
AZD1775 treatment is required.
- Major surgical procedures ?28 days of beginning study treatment, or minor surgical
procedures ?7 days. No waiting period required following port-a-cath or other central
venous access placement.
- Grade >1 toxicity from prior therapy EXCEPT: Alopecia, anorexia, and/or
endocrinopathies on replacement therapy.
- Unable to swallow oral medications. Note: Patient may not have a percutaneous
endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN).
- Known Hepatitis B or C or HIV infection
- Second primary malignancy, other than in situ malignancies or adequately treated basal
cell carcinoma of the skin or other malignancy treated at least 2 years previously
with no evidence of recurrence
- Any of the following cardiac diseases currently or within the last 6 months: unstable
angina pectoris, acute myocardial infarction, congestive heart failure > Class 2 (as
defined by New York Heart Association (NYHA)), conduction abnormality not controlled
with pacemaker or medication, significant ventricular or supraventricular arrhythmias
(patients with chronic rate-controlled atrial fibrillation in the absence of other
cardiac abnormalities are eligible)
- Have had prescription or non-prescription drugs or other products (i.e., grapefruit
juice) known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow
therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4, which
cannot be discontinued 2 weeks before Day 1 of dosing and withheld throughout the
study until 2 weeks after the last dose of study drug
- Co-administration of aprepitant and fosaprepitant during this study is prohibited
- AZD1775 is an inhibitor of breast cancer resistance protein (BCRP). The use of statins
including Atorvastatin which are substrates for BCRP are therefore prohibited and
patients should be moved on to non-BCRP alternatives
- Herbal preparations are not allowed throughout the study. These herbal medications
include, but are not limited to: St. John's wort, kava, ephedra (ma huang), gingko
biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng
- History of Torsades de pointes unless all risk factors that contributed to Torsades
have been corrected
- Mean resting corrected QTc interval using the Fridericia formula (QTcF) >450 msec/male
and >470 msec/female (as calculated per institutional standards) obtained from 1
electrocardiograms (ECGs).