The primary objective of this single arm study is to estimate the progression free survival
of previously-untreated patients with extensive stage small cell lung cancer. Patients will
receive initial chemo-immunotherapy followed by maintenance therapy with durvalumab and oral
- Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
- Age >= 18 years at the time of consent.
- ECOG Performance Status of 0-1 within 14 days prior to registration (Appendix A of
- Histological or cytological confirmed small cell lung carcinoma
- Extensive stage disease
- Patient must be considered suitable to receive a platinum-based chemotherapy as 1st
line treatment for ES-SCLC. Chemotherapy must contain either Carboplatin or Cisplatin
in combination with Etoposide.
- Measurable disease according to RECIST v1.1 for solid tumors within 28 days prior to
- Prior treatment must be completed within the following number of days prior to
--Palliative radiation: for painful bony lesion must be completed prior to
registration and any bone marrow toxicity recovered. For patients who received WBRT,
14 days washout is required prior to study therapy. Patient's must be off steroids
without worsening of symptoms related to brain metastases. Patient should be on stable
doses of anti-convulsant.
- Demonstrate adequate organ function as defined in the protocol; all screening labs to
be obtained within 14 days prior to registration
- Female subjects of childbearing potential and non-sterilized male subjects who intend
to be sexually active during the study must agree to use a highly effective method of
contraception from the time of screening, throughout the total duration of the drug
treatment, and during the 90-day post-drug washout period. See section 188.8.131.52 of the
protocol for full details.
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
- As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study
- Ability to swallow and retain oral medication
- Must have a life expectancy of at least 12 weeks
- Prior systemic therapy for extensive stage or recurrent SCLC
- Patients with recurrent SCLC, who received chemotherapy or definitive chest radiation
in the past for limited-stage SCLC.
- Clinically significant active infection requiring systemic therapy
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
- Participants who have undergone major surgery within 28 days before first dose of
- Participants who are currently receiving any other investigational agents
- Active malignancy requiring therapy other than small cell lung cancer, excluding:
non-melanoma skin cancer, noninvasive colonic polyps, superficial bladder tumors,
cervical cancer in-situ, ductal carcinoma in situ of the breast, monoclonal B-cell
lymphocytosis, or monoclonal gammopathy of undetermined significance.
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg of
prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days
prior to study enrolment. Patient's on physiologic corticosteroid replacement therapy
for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment. Topical, inhaled or intra-articular steroids are not considered as systemic
steroids. Steroids as premedication for hypersensitivity reaction (e.g. CT scan
premedication) or prior to chemotherapy is allowed.
- Active autoimmune or inflammatory disorders (including inflammatory bowel disease
[e.g., colitis or Crohn's disease], systemic lupus erythematosus, or Wegener syndrome
[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,
hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hyperthyroidism or hypothyroidism (e.g., following Hashimoto
syndrome) clinically stable on hormone replacement
- Any chronic skin condition that does not require systemic immunosuppressive
- Patients with celiac disease controlled by diet alone
- Diabetes mellitus with or without insulin replacement therapy
- Has history of immune therapy related pneumonitis that required steroids
- Patients with untreated or symptomatic central nervous system (CNS) metastases or
leptomeningeal carcinomatosis will be excluded. Previously-treated CNS metastases and
have no requirement for steroids for at least 2- week prior to study entry is allowed.
Anticonvulsant therapy at a stable dose is permitted. May have residual symptoms as
new baseline. Brain imaging with either MRI (preferred) or CT with contrast must be
performed on all subjects at screening to evaluate brain metastases.
- Known history of Hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients
positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction
is negative for HCV RNA
- Known history of active tuberculosis
- History of allogeneic stem cell or solid organ transplant
- History of Ataxia telangiectasia
- Uncontrolled intercurrent illness including, but not limited to, serious and active
uncontrolled infection, symptomatic congestive heart failure (NYHA class III-IV),
active inflammatory bowel disease, unstable angina pectoris, uncontrolled seizures, or
psychiatric illness/social situations that would limit compliance with study
- Participants with a known hypersensitivity to durvalumab, ceralasertib or any
excipient of the product
- Patients who have been vaccinated with live, attenuated vaccines within 4 weeks of
first dose of study drug
- Refractory nausea and vomiting, chronic gastrointestinal diseases or previous
significant bowel resection, with clinically significant sequelae that would preclude
adequate absorption of ceralasertib.
- Patients weighing <= 30 Kg.
- Participants may not be receiving any medications or substances that are potent
inhibitors or inducers of CYP3A4 (Appendix B of the protocol).
- There is a required wash-out period of 5 half-lives from such agents prior to
starting ceralasertib, or three weeks for St. John's Wort.
- For non-potent inhibitors or inducers of CYP3A4, the decision to allow a patient
to enroll on the study is per investigator best judgement. Note these include
common azole antifungals, macrolide antibiotics, and other medications listed in
the concomitant medications section. As part of the enrollment/informed consent
procedures, the patient will be counseled on the risk of interactions with other
agents, and what to do if new medications need to be prescribed or if the patient
is considering a new over-the-counter medicine or herbal product.
- Exposure of other drugs metabolized by CYP3A4 and/or CYP2B6 may be reduced and
additional monitoring may be required.
- The use of herbal supplements or 'folk remedies' (and medications and foods that
significantly modulate CYP3A activity) should be discouraged. If deemed
necessary, such products may be administered with caution and the reason for use
documented in the CRF.