Purpose: LY2603618 is a potent and selective inhibitor of the deoxyribonucleic acid (DNA) damage checkpoint kinase 1 (Chk1). It is being developed as a chemotherapeutic-enhancing agent in the treatment of cancer. Ongoing Phase 1 studies have shown the feasibility of combining LY2603618 with either gemcitabine or pemetrexed. The objective of this study is to find the dose of LY2603618 that can be safely combined with standard doses of pemetrexed and cisplatin and to test if this triplet offers a significant improvement in progression-free survival in patients with Stage IV nonsquamous non-small cell lung cancer (NSCLC) in the first-line of palliative treatment.
Arms:
- Phase 1: Experimental
- Cycle 1-2 (21 day cycle):
- Day 1: Pemetrexed 500 mg/m2 and Cisplatin 75 mg/m2
- Day 2: LY2603618 40 – 150 mg/m2
- After 2 cycles, patients may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met.
- Phase 2: Pemetrexed + Cisplatin + LY2603618: Experimental
- Cycle 1-6 (21 day cycle):
- Day 1: Pemetrexed 500 mg/m2 and Cisplatin 75 mg/m2
- Day 2: LY2603618 dose determined from phase 1 portion of trial
- After 6 cycles, patients may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met.
- Phase 2: Pemetrexed + Cisplatin: Active Comparator
- Cycle 1-6 (21 day cycle):
- Day 1: Pemetrexed 500 mg/m2 and Cisplatin 75 mg/m2
- After 6 cycles, patients may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met.