Combination Rucaparib With Nivolumab in Small Cell Lung Carcinoma

Zhonglin Hao

Status and phase

Completed

Phase 2

Conditions

Small Cell Lung Cancer

Treatments

Combination Product: Rucaparib and Nivolumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03958045

49346 MCC-18-LUN-107-CLO

Details and patient eligibility

About

The purpose of this study is to evaluate survival and response rate of the combination rucaparib and nivolumab as maintenance therapy in platinum-sensitive small cell lung carcinoma.

Full description

Small cell lung cancer (SCLC) is one of the most aggressive malignancies with a 5-year survival rate of less than 7%. SCLC is characterized by rapid doubling time, high growth fraction and early development of widespread metastases. SCLC accounts for roughly 93% of all high-grade neuroendocrine carcinomas. The prognosis for SCLC is extremely poor with a median survival less than a year for extensive-stage disease. Therapeutic options have not advanced significantly in over two decades, with frontline treatment consisting of platinum doublet therapy for 3-6 cycles. While most patients show an initial favorable response to Carboplatin/cisplatin + etoposide, this response is usually short-lived. Most patients relapse with resistant disease between 3 to 6 months after completion of initial chemotherapy.

Based on preclinical data supporting the role of immune checkpoint and PARP (poly ADP ribose polymerase ) inhibitors in SCLC, combining nivolumab and rucaparib has the potential to prolong progression-free survival and overall survival. These two classes of drugs have non-overlapping toxicities. This novel combination has not been tried in a front-line maintenance setting for SCLC.

Eligible patients will have pathological (biopsy) or cytologically confirmed stage IV SCLC, and have achieved either partial or complete response post frontline chemotherapy with platinum doublet. Patients will be treated with combination rucaparib and nivolumab. The recommended starting dose of rucaparib as a continuously administered oral monotherapy is 600 mg BID. Nivolumab will be administered as an intravenous infusion once every 4 weeks at a fixed dose of 480 mg. In the absence of treatment delays due to adverse event(s), treatment may continue for 24 months.

Progression-free survival, overall survival, disease control rates, objective response rate, quality of life, and tumor mutation burden will be evaluated during this study (up to 2 years).

Enrollment

33 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Patients with histologically or cytologically confirmed stage IV, extensive stage, small cell lung cancer who achieved either partial or complete remission per RECIST 1.1 post frontline chemotherapy with platinum doublet (Cisplatin or Carboplatin/etoposide).
Enrollment is within 6 weeks of last (4th cycle) of chemotherapy.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Adequate Bone Marrow Function
Adequate Hepatic Function

Exclusion Criteria

Prior therapy with any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints)
Major surgery within 4 weeks of initiation of study medication.
Current use of (some) immunosuppressants
Active infection requiring systemic therapy
HIV/AIDS
Hepatitis B virus or hepatitis C virus infection at screening
Autoimmune disease
Persisting toxicity related to prior therapy
Pregnancy
Vaccination (except inactive) within 4 weeks of the first dose of nivolumab
Hypersensitivity to the study drugs
Cardiovascular disease
Untreated central nervous system (CNS) metastases or leptomeningeal carcinomatosis
(Some) active secondary malignancy
Active pneumonitis or interstitial lung disease