PRISM: PRecIsion in SCLC via a Multicohort Study: Randomized Phase II studies evaluating maintenance Durvalumab with or without Biomarker-Directed Therapy for Extensive Stage Small Cell Lung Cancer (ES-SCLC)

Disease Related Criteria
1. Participants must have histologically or pathologically confirmed diagnosis
of extensive stage small cell lung cancer (ES-SCLC) at the time of protocol entry as defined in Section 4.0.
2. Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
3. Participants must not have a history of limited stage small cell lung cancer.
Prior/Concurrent Therapy Criteria
1. Participants must meet 1 of the following criteria prior to Step 1:
a. Treatment naïve and planning to receive frontline induction treatment with platinum plus etoposide in combination with durvalumab, OR,
b. Have initiated frontline induction therapy and completed at least 1 (≥ 1) cycle and at most 3 (≤ 3) cycles of platinum and etoposide.
At most 2 (≤ 2) of these cycles could have been given without durvalumab. See Table 1 for allowable cycles of platinum/etoposide and durvalumab.
Table 1. Allowable combined cycles of treatment
# Cycles of
platinum/etoposide
# Cycles of durvalumab
1 0-1
2 0-2
3 1-3
NOTE: Participants must not have received immunotherapy other than durvalumab (e.g., atezolizumab) prior to enrollment.
2. Participants must not have received any anti PD-1 or anti PD-L1 (including durvalumab [MEDI4736]) treatment for SCLC prior to starting frontline induction treatment for ES-SCLC.
3. Participants must not have received anti PD-1 or anti PD-L1 other than durvalumab (MEDI4736) as part of frontline induction treatment for ESSCLC. Participants must have not received atezolizumab, pembrolizumab, or nivolumab as part of frontline induction treatment.
4. Participants must not have received any investigational agent for the treatment of ES-SCLC.
5. Participants must not be planning to receive any concurrent non-protocol directed chemotherapy, immunotherapy, biologic or hormonal therapy for SCLC treatment while receiving treatment on this study. This includes nonprescription supplements, alternative treatments or vitamins other than a
standard multivitamin. NOTE: If participant has bone metastases, bisphosphonates are allowed.
6. Participants must not have any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, and
vitiligo.
Clinical/Lab Criteria
1. Participants must be ≥ 18 years old at the time of Step 1 Registration.
2. Participants must be able to safely receive the frontline induction treatment with platinum plus etoposide in combination with durvalumab described in Section 7.1, per the current FDA-approved package insert(s), institutional guidelines, and the treating investigator’s discretion
3. Participants must have Zubrod Performance Status of 0-2 within 28 days prior to Step 1 Registration (see Section 10.4).
4. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator within 28 days prior to Step 1 Registration.
5. Participants must not have had an allogenic organ transplantation.
6. Participants must not have medical contraindications to receiving immunotherapy, including history of non-infectious pneumonitis that required steroids or active autoimmune disease that has required systemic
treatment with disease modifying agents, corticosteroids or immunosuppressive drugs in the past two years. Replacement therapy (e.g. thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Intra-articular steroid injections are allowed.
7. Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method during protocol therapy and for 6 months following completion of protocol therapy with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with
testing showing no sperm in the semen. Participants should not breastfeed during protocol therapy and for 6 months following completion of protocol therapy.
Specimen Submission Criteria
1. Participants must have adequate tumor tissue available from SCLC
defined in Section 15.2 and agree to have these tissue specimens
submitted per Section 15.2. Participants must agree to have any leftover tissue (tissue that remains after subtype and biomarker testing) retained for the use of future correlative studies.