Background: Maintenance therapy is a promising therapeutic approach for extensive-stage small cell lung cancer (ES-SCLC), especially in light of IMpower 133 (Horn NEJM 2018). SCLC models of poly (ADP-ribose) polymerase (PARP) protein 1 and 2 inhibition suggested synergy with temozolomide (TMZ) (Wainberg AACR 2016). Combining PARP inhibition and TMZ with atezolizumab after first-line therapy for ES-SCLC may improve disease control. Methods: This is a phase 1b/2, randomized, open-label study of TMZ plus niraparib, a PARP inhibitor, with atezolizumab versus atezolizumab as maintenance therapy in adult patients with ES-SCLC after completion of platinum-based first-line chemotherapy. The primary outcome for phase 1b is the RP2D of TMZ in combination with niraparib, and for phase 2, progression-free survival (PFS). Secondary endpoints include safety, objective response rate, and overall survival. Exploratory endpoints include adverse events and patient-reported outcomes, including health-related quality of life. Phase 1b participants are required to have an advanced and incurable solid malignancy. Part one of phase 1b includes an accelerated lead-in of 12 participants treated in cohorts of 6 with an initial dose level of niraparib 200 mg po daily in 28-day cycles and low-dose TMZ 40 mg po daily on days 1-5 of each cycle. Part two includes a safety lead-in of 6 patients receiving standard-of-care atezolizumab, to which R2PD niraparib and TMZ will be added. For phase 2, participants are required to have ES-SCLC with a complete response or partial response per RECIST 1.1 following 4 to 6 cycles of platinum-based chemotherapy and ability to proceed to randomization within 7 weeks after day 1 of the last cycle of prior chemotherapy. Prophylactic WBRT is allowed prior to study. 52 participants will be stratified by a history of brain metastases and randomized 1:1 to atezolizumab with or without RP2D niraparib plus TMZ. There will be no cross-over between arms. To date, cohort 1 had two DLTs. Enrollment to dose level -1 and an intermediate dose have been completed without a DLT. The atezolizumab safety lead-in begins enrollment in March 2020. Clinical trial information: NCT03830918