Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
| Ref Type | Journal Article | ||||||||||||
| PMID | (34478166) | ||||||||||||
| Authors | Ramalingam SS, Thara E, Awad MM, Dowlati A, Haque B, Stinchcombe TE, Dy GK, Spigel DR, Lu S, Iyer Singh N, Tang Y, Teslenko I, Iannotti N | ||||||||||||
| Title | JASPER: Phase 2 trial of first-line niraparib plus pembrolizumab in patients with advanced non-small cell lung cancer. | ||||||||||||
|
|||||||||||||
| URL | |||||||||||||
| Abstract Text | Poly(ADP-ribose) polymerase (PARP) inhibitors may synergize with programmed cell death receptor-1 (PD-1) inhibitors to enhance adaptive and innate antitumor immune responses. In the phase 2 JASPER study (NCT04475939), the PARP inhibitor niraparib was evaluated in combination with the PD-1 inhibitor pembrolizumab in patients with metastatic and/or locally advanced non-small cell lung cancer (NSCLC).Patients whose tumors had programmed cell death ligand 1 (PD-L1) tumor proportion scores (TPS) ≥50% (cohort 1) or 1%-49% (cohort 2) received first-line niraparib (200 mg once daily) plus pembrolizumab (200 mg every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR). Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics.Thirty-eight patients were enrolled in cohorts 1 and 2. In cohort 1, ORR (95% confidence interval [CI]) was 56.3% (9 of 16 patients; 29.9%-80.2%); 2 of 16 patients had complete responses and 7 of 16 had partial responses (PRs). In cohort 2, ORR was 20.0% (5.7%-43.7%) with 4 of 20 PRs. In cohorts 1 and 2, the median DoR was 19.7 months (95% CI, 4.2 months to not estimable [NE]) and 9.4 months (95% CI, 4.2 months to NE), the median PFS was 8.4 months (95% CI, 3.9-22.1 months) and 4.2 months (95% CI, 2.0-6.2 months), and the median OS was NE (95% CI, 6.0 months to NE) and 7.7 months (95% CI, 4.0-12.5 months), respectively. Grade ≥3 treatment-emergent adverse events occurred in 88.2% and 85.7% of patients in cohorts 1 and 2, respectively. Safety was consistent with known profiles of single-agent niraparib and pembrolizumab.Niraparib plus pembrolizumab showed clinical activity in patients with advanced and/or metastatic NSCLC.The JASPER clinical trial studied a new combination treatment for advanced or metastatic non-small cell lung cancer (NSCLC). Pembrolizumab, a drug approved for NSCLC, was given with niraparib. Previous research showed that these 2 drugs together might work better than either drug alone. This study found that more than half of patients with high levels of a tumor marker responded to the combination, and one-fifth of patients with lower levels of the marker responded. The types of side effects from the combination were similar to side effects from both drugs alone. These results support more research on this combination. | ||||||||||||
| Molecular Profile | Treatment Approach |
|---|
| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
|---|
| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
|---|
| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|
| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
|---|
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| CD274 over exp | lung non-small cell carcinoma | predicted - sensitive | Niraparib + Pembrolizumab | Phase II | Actionable | In a Phase II trial, combination Zejula (niraparib) and Keytruda (pembrolizumab) resulted in an objective response rate (ORR) of 56.3% (9/16; 2 complete, 7 partial responses), 19.7-mo median duration of response (mDR), and 8.4-mo median progression-free survival (mPFS) in non-small cell lung cancer patients with a CD274 (PD-L1) TPS>=50%, and an ORR of 20% (4/20; 4 partial responses), 9.4-mo mDR, and 4.2-mo mPFS in patients with a CD274 (PD-L1) TPS=1-49% (PMID: 34478166; NCT03308942). | 34478166 |
| CD274 positive | lung non-small cell carcinoma | predicted - sensitive | Niraparib + Pembrolizumab | Phase II | Actionable | In a Phase II trial, combination Zejula (niraparib) and Keytruda (pembrolizumab) resulted in an objective response rate (ORR) of 56.3% (9/16; 2 complete, 7 partial responses), 19.7-mo median duration of response (mDR), and 8.4-mo median progression-free survival (mPFS) in non-small cell lung cancer patients with a CD274 (PD-L1) TPS>=50%, and an ORR of 20% (4/20; 4 partial responses), 9.4-mo mDR, and 4.2-mo mPFS in patients with a CD274 (PD-L1) TPS=1-49% (PMID: 34478166; NCT03308942). | 34478166 |