Randomized phase II study of nivolumab (N) alone versus with pegilodecakin (PEG) in combination with N in patients (pts) with post-platinum immunotherapy-naive stage IV non-small cell lung cancer (NSCLC) and no or low PD-L1 expression (CYPRESS 2).

e21744 Background: Nivolumab (N) is an immune checkpoint inhibitor (CPI) approved to treat post-platinum NSCLC as monotherapy. PEG in combination with N has demonstrated promising efficacy in NSCLC pts in a phase I trial (IVY; NCT02009449; Naing et al., 2019 Lancet Oncol), providing rationale for this randomized phase II trial (CYPRESS 2). Methods: CYPRESS 2 was an open label phase II trial, for ECOG 0-1, PD-L1 negative or low (TPS 0-49%), Stage IV NSCLC pts, without known EGFR/ALK mutations. Pts were randomized 1:1 to arm N (240 mg every 14-days or 480 mg every 28-days as decided by investigator) v. arm PEG+N (received N as above + PEG daily of 0.8 mg if weight ≤80kg and 1.6mg if weight > 80 kg). Pts were stratified by tumor histology and smoking history and must have no prior history of cancer or CPI therapy. Primary endpoint was ORR (per RECIST v 1.1 per investigator). Secondary endpoints included PFS, OS, and safety. Exploratory endpoints included immune activation biomarkers (baseline and change from baseline), assessed by immunoassay. Results: As of Aug 28, 2019, 52 pts were randomized to PEG+N (n=27) or N (n=25). Median follow-up time was 11.6 months. The following results were found for PEG+N versus N: ORR 14.8% v. 12.0%, mPFS 1.9 v. 1.9 months with HR = 1.01 (95% CI [0.52, 1.95]), mOS 6.7 v. 10.7 months with HR = 1.87 (95% CI [0.77, 4.53]). Gr ≥3 treatment related adverse events (TRAEs) for PEG+N versus N were 70.4% vs. 16.7%. Gr 3 TRAEs of ≥10% incidence included anemia (40.7% v. 0%), fatigue (18.5% v. 0%), and thrombocytopenia (14.8% v. 0%). In PEG+N arm, increased circulating IL-18, Granzyme B, FasL, and IFNg levels and decreased TGFb levels were observed on treatment. Conclusions: Exploratory pharmacodynamic results were consistent with immunostimulatory signals of the IL-10R pathway. Despite evidence of biological effect, adding PEG to N did not lead to improvement in ORR, PFS, or OS in post-platinum advanced NSCLC with no or low PD-L1 expression. PEG+N arm demonstrated expected safety profile but overall higher toxicity compared to nivolumab alone. Clinical trial information: NCT03382912.

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Randomized phase II study of pembrolizumab (P) alone versus pegilodecakin (PEG) in combination with P as first-line (1L) therapy in patients (pts) with stage IV non-small cell lung cancer (NSCLC) with high PD-L1 expression (CYPRESS 1).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.9563 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 9563-9563

Author(s):

David R. Spigel ◽

Merrill Kingman Shum ◽

Jeffrey Gary Schneider ◽

Robert M. Jotte ◽

Jennifer L. Eisenstein ◽

...

Keyword(s):

Phase Ii ◽

Advanced Nsclc ◽

Phase Ii Trial ◽

Stage Iv ◽

Prior History ◽

P Value ◽

Open Label ◽

Randomized Phase Ii ◽

Open Label Phase ◽

Treatment Naïve

9563 Background: Pembrolizumab (P) is an immune checkpoint inhibitor (CPI) approved to treat 1L advanced NSCLC pts with high PD-L1 expression. PEG + CPI has demonstrated promising efficacy in NSCLC pts in a phase I trial (IVY; NCT02009449; Naing et al., 2019 Lancet Oncol), providing rationale for this randomized phase II trial (CYPRESS 1; NCT03382899). Methods: CYPRESS 1 was an open label phase II trial, for treatment-naïve, ECOG 0-1, PD-L1 high (22C3 clone TPS ≥ 50%), Stage IV NSCLC pts, without known EGFR/ALK mutations. Pts were randomized 1:1 to arm P (received 200mg IV on day 1 of a 21-day cycle) v. arm PEG+P (received P as above + PEG daily of 0.8 mg if weight ≤80kg and 1.6mg if weight> 80 kg up to 35 cycles in each arm). Pts were stratified by tumor histology and must have no prior history of cancer or prior CPI therapy. Primary endpoint was ORR (per RECIST v1.1 by investigator) Secondary endpoints included PFS, OS, and safety. Exploratory endpoints included ORR and PFS by blinded independent central review (BICR). Immune activation biomarkers (baseline and change from baseline) were assessed by serum immunoassay, IHC, and sequencing. Results: As of Dec 6, 2019, 101 pts were randomized to PEG+P (n=51) or P (n=50). Median follow-up time was 10.0 months (95% CI [8.4, 11.1]). Results for PEG+P versus P were: ORR per investigator was 47% v. 44% (p=0.76), ORR per BICR was 53% v. 46%(p=0.78), mPFS per investigator was 6.3 v. 6.1 months with HR = 0.94 (95% CI [0.54, 1.63];p=0.82), mPFS per BICR was 6.4 v. 7.2 months with HR = 1.10 (95%CI [0.62, 1.96]; p=0.74), and mOS was 16.3 months v. not reached with HR = 1.36 (95% CI [0.66, 2.77]; p-value=0.40). Gr ≥3 treatment related adverse events (TRAEs) were 62% for PEG+P versus 19% for P. Gr ≥3 TRAEs with ≥10% incidence included anemia (20% vs. 0%) and thrombocytopenia (12% vs. 2%). Biomarker data on immunostimulatory signals of the IL-10R pathway will be included. Conclusions: Adding PEG to P did not lead to improvement in ORR, PFS, or OS, in 1L advanced NSCLC with high PD-L1 expression. PEG+P arm demonstrated expected safety profile but overall higher toxicity compared to pembrolizumab alone. Clinical trial information: NCT03382899 .

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Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial

BMC Cancer ◽

10.1186/s12885-020-07055-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Relinde I. Y. Lieverse ◽

Evert J. Van Limbergen ◽

Cary J. G. Oberije ◽

Esther G. C. Troost ◽

Sine R. Hadrup ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Stage Iv ◽

Standard Of Care ◽

Open Label ◽

Stereotactic Ablative Body Radiotherapy ◽

Open Label Phase ◽

Randomised Controlled ◽

Nsclc Patients

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A multicenter, randomized phase II trial of gemcitabine and oxaliplatin (GEMOX) alone or in combination with biweekly cetuximab in the first-line treatment of advanced biliary cancer: Interim analysis of the BINGO trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4520 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4520-4520 ◽

Cited By ~ 1

Author(s):

D. Malka ◽

T. Trarbach ◽

L. Fartoux ◽

J. Mendiboure ◽

C. de la Fouchardière ◽

...

Keyword(s):

Phase Ii ◽

Interim Analysis ◽

Palliative Chemotherapy ◽

Phase Ii Trial ◽

Performance Status ◽

Biliary Cancer ◽

Open Label ◽

Standard Regimen ◽

Randomized Phase Ii ◽

Secondary Endpoints

4520 Background: There is no standard regimen for palliative chemotherapy of advanced biliary cancers. The GEMOX regimen is an option (BJC 2008). EGFR over-expression has been observed in advanced biliary cancers suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with advanced biliary cancer, WHO performance status 0–1, and without prior palliative chemotherapy were eligible for this international, open-label, two-stage, randomized phase II trial. Patients received GEMOX (gemcitabine, 1000 mg/m2 [10 mg/m2/min] at day [D]1; oxaliplatin, 100 mg/m2 at D2) alone (arm A) or with cetuximab (500 mg/m2 at D1 or 2, arm B), every 2 weeks. Randomization was stratified according to tumor stage and location, center, and prior treatments. The primary endpoint was 4-month crude progression-free survival (PFS) rate (H0 hypothesis, < 40%; H1, ≥ 60%; planned sample size, 50 patients per arm). Secondary endpoints were response rate, PFS, overall survival, toxicity, early response assessment by PET, and blood/tumor EGFR signalling pathway member analyses. A data safety monitoring board-approved interim analysis was performed at the end of the first stage (18 patients per arm, minimal follow- up 4 months). Results: From October 2007 to October 2008, we enrolled 101 patients (median age, 62 yrs; male, 60%; metastatic, 86%; non-gallbladder, 76%). Among the 36 patients at the time of the interim analysis, the median number of treatment cycles was 6 and 8 in arms A and B, respectively. 76% (arm A) and 67% (arm B) had NCI-CTC grade 3–4 toxicity, mainly cytopenia (41%/39%), peripheral neuropathy (modified Levi's scale grade 2–3: 29%/33%), fatigue (6%/22%), gastrointestinal toxicity (12%/17%), and rash/hypersensitivity (0%/17%). The 4-month PFS rate was 44% (95% CI, 20–70) and 61% (95% CI, 36–83) in arms A and B, respectively. Conclusions: The GEMOX-cetuximab regimen seems well tolerated in patients with advanced biliary cancer. Adding cetuximab to GEMOX showed promising activity and therefore the trial was continued. Updated results on the whole population for primary and secondary endpoints will be available at the meeting. [Table: see text]

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Phase II study of pemetrexed (P) plus carboplatin (Cb) or cisplatin (C) with concurrent radiation therapy followed by pemetrexed consolidation in patients (pts) with favorable-prognosis inoperable stage IIIA/B non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.7002 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 7002-7002

Author(s):

Hak Choy ◽

Lee Steven Schwartzberg ◽

Shaker R. Dakhil ◽

Edward B. Garon ◽

Janak K. Choksi ◽

...

Keyword(s):

Radiation Therapy ◽

Phase Ii ◽

Overall Response Rate ◽

Phase Ii Trial ◽

Complete Response ◽

Time To Progression ◽

Stage Iiia ◽

Open Label ◽

Randomized Phase Ii ◽

Secondary Endpoints

7002 Background: There is no consensus chemotherapy regimen with concurrent radiation therapy (CRT) for inoperable stage IIIA/B NSCLC. P synergizes with ionizing radiation, as well as with Cb and C in preclinical models. These doublets have shown efficacy and favorable toxicity profiles in phase II/III trials. Methods: In this open-label randomized phase II trial, 98pts with inoperable stage IIIA/B NSCLC (all histologies) were randomized (1:1) to P 500 mg/m2 plus Cb AUC 5 (PCb) or P 500 mg/m2 plus C 75 mg/m2 (PC) intravenously (IV) every 21 days for 3 cycles. All pts received CRT 64–68 Gy (2 Gy/day, 5 days/week, Days 1–45). Consolidation P 500 mg/m2 IV every 21 days for 3 cycles began 3 weeks after completion of CRT. The primary endpoint was 2-year overall survival (OS); secondary endpoints included median OS, time to progression (TTP), overall response rate (ORR), and toxicity. Results: Since Jun 2007, 98 pts were enrolled (PCb: 46; PC: 52).Pts were followed until Oct 2011. Mean dose compliance was PCb: 95.7% P, 97.1% Cb; PC: 89.7% P, 89.1% C. Mean dose compliance for CRT was PCb: 95.7%; PC: 88.1%. CRT dose interruptions occurred in PCb: 32.6% and PC: 40.4%. Two-year OS was PCb: 45.2% (95% confidence interval [CI], 29.3-59.8); PC: 57.6% (95% CI, 41.6-70.7); p=0.270. Median OS (months) was PCb: 18.7 (95% CI, 12.9-not assessable [N/A]); PC: 27.0 (95% CI, 23.2-N/A). Median TTP (months) was PCb: 8.8 (95% CI, 6.0-10.7); PC: 13.1 (95% CI, 8.3-N/A); p=0.057. The ORR rates were PCb: 52.2% (complete response [CR], 6.5%; partial response [PR], 45.7%); PC: 46.2% (CR, 3.8%; PR, 42.3%). Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. No drug-related deaths were reported. Conclusions: While conclusions are limited by the size of the trial, this study suggests OS and TTP advantages for the C-containing arm. Both combinations with CRT appear well tolerated.

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