Sindilimab combined with nab-paclitaxel plus gemcitabine as first-line treatment for patients with advanced pancreatic cancer.

e16257 Background: This study aimed to evaluate the efficacy and safety of Sindilimab combined with nab-paclitaxel plus gemcitabine as first-line treatment for advanced pancreatic cancer. Methods: This was a single-arm, simple-center, exploratory trial, which included advanced pancreatic cancer pts. Patients received Sindilimab combined with nab-paclitaxel plus gemcitabine. Combined chemotherapy lasted for no more than 12 cycles. Once chemotherapy intolerance occurred or at end of 12-cycle combined chemotherapy, pts with stable disease or objective response would continue to take Sindilimab as single agent until disease progression or intolerable toxicity. Response was assessed every 8 weeks. Results: 16 eligible patients were enrolled and 14 pts were evaluable for efficacy analysis. Baseline characteristics are shown in Table 2. Conclusions: This study has showed high anti-tumor efficacy and tolerant toxicity in first-line regimen for advanced pancreatic cancer. Furthermore, it is needed to be proved in update results and large scale studies. Efficacy As shown in Table 3, among 14 evaluable pts, unconfirmed ORR was 57.1% and DCR was 92.8%. 8 pts got partial response (PR), 5 pts stable disease (SD) and 1 pts progressive disease(PD) at best. PFS: The primary endpoint 6-month PFS rate was 2%(95% CI 50.4%-72.4%). Which indicated that the primary endpoint of the study was reached. And mPFS was 7.3 months(95% CI 5.9-8.1). OS: Median OS was not reached and 6m-OS rate was 85.7% (95%CI 5%-91.3%). Safety. All 16 pts were included in the safety analysis (Table 4). The overall AE incidence rate was 93.75% .≥Grade 3 irAE included GGT increased (37.5%) and peripheral neuropathy (6.25%). No TRAE led to death.[Table: see text][Table: see text][Table: see text][Table: see text]

Download Full-text

SHR-1210 combined with GEMOX as first-line treatment in patients with advanced biliary tract cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.535 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 535-535 ◽

Cited By ~ 1

Author(s):

Xiaofeng Chen ◽

Xiaofeng Wu ◽

Hao Wu ◽

Qianwen Shao ◽

Feipeng Zhu ◽

...

Keyword(s):

Biliary Tract ◽

Primary Endpoint ◽

Stable Disease ◽

Biliary Tract Cancer ◽

Combined Chemotherapy ◽

Line Treatment ◽

First Line ◽

Tract Cancer ◽

Grade 3 ◽

First Line Treatment

535 Background: This study aimed to evaluate the efficacy and safety of SHR-1210 (a humanized anti-programmed cell death receptor 1 antibody) plus gemcitabine and oxaliplatin (GEMOX) as first line treatment in patients (pts) with biliary tract cancer (BTC). Methods: This was a single-arm, single-center, exploratory trial, which included advanced BTC pts. Pts received SHR-1210 (3mg/kg, total dose ≤200mg, ivd, D1/2W) combined with gemcitabine (800 mg/m2, ivd, D1/2W) and oxaliplatin (85mg/m2, ivd, D2/2W). Combined chemotherapy lasted for no more than 12 cycles. Once chemotherapy intolerance occurred or at end of 12-cycle combined chemotherapy, pts with stable disease or objective response would continue to take SHR-1210 as single agent until disease progression or intolerable toxicity. The primary endpoint was the 6-month progression free survival (PFS) rate. Results: From February 2018 to April 2019, 37 eligible pts were enrolled. The median age was 64 (range 41-74) years, male/female was 70.3/29.7%, and bile duct cancer/gallbladder cancer was 59.5/40.5%. All 37 pts were included in the safety analysis. The overall AE incidence rate was 97.3%. The incidence of grade ≥3 AEs was 73.0%, which mainly included increased GGT (gammaglutamyltransferase, 18.9%), hypokalemia (18.9%), and fatigue (16.2%). Particularly, the incidence of fever is 73.0%, in which 2 pts experienced grade 3/4 fever. Among 36 evaluable pts, 19 pts got partial response (PR, 52.8%), 14 pts stable disease (SD, 38.9%), and 3 pts progressive disease (PD, 8.3%) at best. The primary endpoint 6-month PFS rate was 50.0% (95% CI 32.4-65.4), which indicated that the primary endpoint of the study was reached, and mPFS was 6.2 months (95% CI 4.2-7.1). The 12-month overall survival (OS) rate was 50.5% (95% CI 30.6-67.4), and mOS was 12.1 months (95% CI 8.0-NA). Conclusions: This study has reached the pre-defined primary endpoint with a high response rate. Predictive biomarker analysis was reported in another abstract. Further study is needed to validate the efficacy of this combination. Clinical trial information: NCT03486678.

Download Full-text

Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Single-Agent Gemcitabine As First-Line Treatment of Patients With Advanced Pancreatic Cancer: The GIP-1 Study

Journal of Clinical Oncology ◽

10.1200/jco.2009.25.4433 ◽

2010 ◽

Vol 28 (10) ◽

pp. 1645-1651 ◽

Cited By ~ 198

Author(s):

Giuseppe Colucci ◽

Roberto Labianca ◽

Francesco Di Costanzo ◽

Vittorio Gebbia ◽

Giacomo Cartenì ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Single Agent ◽

Advanced Pancreatic Cancer ◽

Phase Iii ◽

Hematologic Toxicity ◽

Line Treatment ◽

First Line ◽

Phase Iii Trial ◽

First Line Treatment

PurposeSingle-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696).Patients and MethodsPatients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) ≥ 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m2weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m2added weekly to gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral α .05, 355 events were needed and 400 patients planned.ResultsFour hundred patients were enrolled (arm A: 199; arm B: 201). Median age was 63, 59% were male, 84% had stage IV, and 83% had KPS ≥ 80. Median overall survival was 8.3 months versus 7.2 months in arm A and B, respectively (HR, 1.10; 95% CI, 0.89 to 1.35; P = .38). Median progression-free survival was 3.9 months versus 3.8 months in arm A and B, respectively (HR, 0.97; 95% CI, 0.80 to 1.19; P = .80). The objective response rate was 10.1% in A and 12.9% in B (P = .37). Clinical benefit was experienced by 23.0% in A and 15.1% in B (P = .057). Combination therapy produced more hematologic toxicity, without relevant differences in nonhematologic toxicity.ConclusionThe addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.

Download Full-text

Immunomodulatory effects of lenalidomide in combination with gemcitabine as first-line treatment in patients with advanced pancreatic cancer

Annals of Oncology ◽

10.1093/annonc/mdv514.26 ◽

2015 ◽

Vol 26 ◽

pp. viii5

Author(s):

M. Liljefors ◽

F.S. Mozaffari ◽

H. Mellstedt ◽

G. Ullenhag

Keyword(s):

Pancreatic Cancer ◽

Advanced Pancreatic Cancer ◽

Line Treatment ◽

Immunomodulatory Effects ◽

First Line ◽

First Line Treatment

Download Full-text

Gemcitabine and oxaliplatin combination as first-line treatment for advanced pancreatic cancer: a multicenter phase II study

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-008-0873-9 ◽

2008 ◽

Vol 64 (2) ◽

pp. 317-325 ◽

Cited By ~ 11

Author(s):

Kyung Hee Lee ◽

Min Kyoung Kim ◽

Yeol Hong Kim ◽

Baek Yeol Ryoo ◽

Ho Yeong Lim ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Advanced Pancreatic Cancer ◽

Line Treatment ◽

First Line ◽

Multicenter Phase ◽

First Line Treatment

Download Full-text

Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15111 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15111-15111 ◽

Cited By ~ 1

Author(s):

Y. Park ◽

S. Yi ◽

H. Kim ◽

S. Lee ◽

I. Hwang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Stable Disease ◽

Single Agent ◽

Advanced Pancreatic Cancer ◽

Median Number ◽

Line Treatment ◽

Second Line ◽

Best Response ◽

Grade 3 ◽

Number Of Cycles

15111 Background: The aim of this phase II study was to determine whether second line therapy with single agent irinotecan could provide any clinical benefit in patients with gemcitabine- pretreated advanced pancreatic cancer. Methods: From January 2004 to October 2006, patients with advanced pancreatic cancer previously treated with gemcitabine alone or combination were treated with single agent irinotecan(150 mg/m2, biweekly), until unacceptable toxicity or disease progression. Primary endpoint was response rate with single stage design. Results: Twenty-eight patients were enrolled(22 male, 6 female, median age : 54.5 years (39–76)). Nine patients are still alive and 3 remain on therapy with stable disease. The median number of cycles was 3.5(1–12). Twenty-four patients were assessable for toxicity and 21 for response. The most common toxicities was diarrhea (grade 3, 12.5%). Grade 3 neutropenia in 1 patient was observed. Other hematological and non-hematological toxicities were mild and manageable. Partial responses were observed in 3 patients (3/21, 14%). An additional 9 patients (9/21, 43%) had stable disease as their best response. 12 patients have progressed with a median time-to-progression of 4.0 months. Conclusions: Single-agent irinotecan was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced pancreatic cancer, refractory to gemcitabine. No significant financial relationships to disclose.

Download Full-text

A phase II study of lapatinib and capecitabine in first-line treatment of metastatic pancreatic cancer (ICORG 08- 39).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.315 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 315-315 ◽

Cited By ~ 2

Author(s):

R. S. McDermott ◽

P. Calvert ◽

M. Parker ◽

G. Webb ◽

B. Moulton ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Advanced Pancreatic Cancer ◽

Metastatic Pancreatic Cancer ◽

Survival Duration ◽

Synergistic Activity ◽

Line Treatment ◽

First Line ◽

First Line Treatment

315 Background: The combination of capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer patients has proved beneficial in terms of median survival duration, objective radiological response rate and decrease in tumour marker levels from baseline. In the phase I study of capecitabine and lapatinib carried out in advanced solid tumors, the optimal tolerated regimen was determined to be lapatinib 1,250 mg plus capecitabine 2,000 mg/m2/day. At these dose levels, the combination was well tolerated with few grade 3 toxicities and no grade 4 toxicity. Our preclinical work suggested synergistic activity of capecitabine and lapatinib in pancreatic cancer. We initiated a study of this combination in the first-line therapy of metastatic pancreas cancer. Methods: This was a single-arm multicenter study in patients with chemotherapy-naive metastatic pancreatic cancer. The primary endpoint was overall survival. The study was designed as a Simons two-stage optimal design and was divided into two stages. The first stage was to recruit up to 12 patients. If at least seven of these patients survived for at least six months, then a further 20 patients would be enrolled into the study. If six or fewer of the initial 12 patients met the specified study survival criteria, the study would be halted. Treatment was to be administered until disease progression or until withdrawal from the study due to unacceptable toxicity or other reasons. Clinical and laboratory parameters were assessed to evaluate disease response and toxicity of therapy. The study patients received lapatinib 1,250 mg/day, plus capecitabine 2000 mg/m2/day on days 1-14 every 21 days. Results: Nine patients were enrolled. Seven of these patients did not achieve the interim protocol response requirement of survival for at least 6 months, to allow for the study to continue to the second cohort of patients. Median overall survival from first dose was 4 months. Median time on treatment was 2 months. There were no objective responses. There were no unexpected toxicities. Conclusions: The addition of lapatinib to capecitabine does not improve overall survival in the first-line treatment of advanced pancreatic cancer patients. [Table: see text]

Download Full-text

Activity of RX-3117, an oral antimetabolite nucleoside, in patients with pancreatic cancer: Preliminary results of stage 1 of the phase 1a/2b.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.445 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 445-445 ◽

Cited By ~ 1

Author(s):

Drew W. Rasco ◽

Christine Peterson ◽

Ely Benaim ◽

Jaime R. Merchan

Keyword(s):

Pancreatic Cancer ◽

Primary Endpoint ◽

Stable Disease ◽

Performance Status ◽

Single Agent ◽

Advanced Pancreatic Cancer ◽

Metastatic Pancreatic Cancer ◽

Cancer Data ◽

Phase 1B ◽

Stage 1

445 Background: RX-3117 is an oral smallmolecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 1 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 1 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle in a 2-stage Simon design. Eligible subjects (aged ≥ 18 years) were those with relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% (2 out of 10 subjects) rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% (1 of 10 subjects) with a partial response rate or better. Results: As of Sep 2016, 8 out of 10 subjects have been enrolled (4 females, 4 males), the mean age was 70 years, ECOG performance status was 1 and 5 subjects had received more than 4 prior therapies. Two subjects met the primary endpoint of stable disease with a duration of 140-168 days at the time of this submission. The most frequent adverse events were moderate to severe anemia, mild to moderate fatigue, abdominal pain and diarrhea. Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. As the primary endpoint has been achieved, the study will now move to stage 2 where an additional 40 subjects with advanced pancreatic cancer will be enrolled. Clinical trial information: NCT02030067.

Download Full-text

RXÂ 3117: Activity of an oral antimetabolite nucleoside in subjects with pancreatic cancerâ€“Preliminary results of stage II of the phase Ia/IIb study.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.396 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 396-396

Author(s):

Vincent M. Chung ◽

Jaime R. Merchan ◽

Allyson J. Ocean ◽

Drew W. Rasco ◽

Hani M. Babiker ◽

...

Keyword(s):

Pancreatic Cancer ◽

Partial Response ◽

Primary Endpoint ◽

Stable Disease ◽

Single Agent ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

Cancer Data ◽

Phase 1B

396 Background: RX-3117 is an oral small-molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 2 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 2 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle. Eligible subjects (aged ≥ 18 years) had relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% of evaluable subjects with a partial response rate or better. Results: As of Sep 2017, 44 subjects have been enrolled (22 females, 22 males). The median age was 68 years, ECOG performance statuses were 0 (13 subjects) and 1 (31 subjects) and 6 subjects had received 4 or more prior therapies. One subject had an unconfirmed partial response and 21 subjects met the primary endpoint of stable disease with a duration of 30-224 days. The most frequent adverse events were mild to moderate anemia (19%), mild to moderate fatigue (15%), mild to moderate diarrhea (11%), and severe anemia (9%). Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. The study continues to enroll subjects with advanced pancreatic cancer into stage 2. A phase 2 study with nab-paclitaxel in first-line patients with advanced pancreatic cancer has been started. Clinical trial information: NCT02030067.

Download Full-text

PD-1 antibody combined with paclitaxel (albumin bound) and gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps4665 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS4665-TPS4665

Author(s):

Jiujie Cui ◽

Jiayu Yao ◽

Yu Wang ◽

Yiyi Liang ◽

Yongchao Wang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Checkpoint Inhibitors ◽

Tumor Therapy ◽

Advanced Pancreatic Cancer ◽

Metastatic Pancreatic Cancer ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

First Line Treatment

TPS4665 Background: Pancreatic cancer is a malignant tumor with limited therapeutic strategies and poor prognosis. About 60% of the patients have metastasis disease at time of diagnosis and lose the opportunity for surgery. Thus, therapy based on drugs becomes a vital part in pancreatic cancer. In 2013, MPACT showed that albumin-bound paclitaxel combined with gemcitabine in the treatment of metastatic pancreatic cancer could increase the mOS from 6.6 months to 8.7 months (HR = 0.72, 95% CI: 0.62-0.83; P < 0.001). Nowadays, the immunosuppressive checkpoint inhibitors acting on PD-1/PD-L1 pathway have shown a significant efficacy in enhancing tumor immune surveillance and anti-tumor immune response. In 2018, two studies reported in ASCO showed the preliminary efficacy of albumin paclitaxel, gemcitabine and PD-1 inhibitor in the treatment of advanced pancreatic cancer. Among patients who have not received treatment before, the disease control rate was even up to 100%. Therefore, this study will further explore the domestic PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as the first-line treatment of advanced pancreatic cancer among Chinese pancreatic cancer patients. Methods: This is a prospective, single-armed, exploratory, investigator initiated trial to explore the efficacy and safety of PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as first-line treatment of metastatic pancreatic cancer. This study is, to our knowledge, the first one to test the efficacy and safety of PD-1 antibody on metastatic pancreatic cancer patients among Chinese population. Survival index is median survival estimated by Kaplan-Meier and draw the survival curve. The response rate was compared by χ 2 test / Fisher test. All primary and secondary outcomes will be analyzed on the full analysis set. PD-1 antibody, 200mg, D1 administration; paclitaxel (albumin binding type), 125mg/m2, D1, 8 days administration; gemcitabine, 1000mg/m2, D1, 8 days administration, every 21 days as a cycle and PD-1 antibody (200mg, D1, every 21 days) single drug maintenance treatment is given after the completion of 6 cycle chemotherapy. Major eligibility criteria is that each participant must have metastatic pancreatic cancer confirmed by histology or cytology and has never received systemic anti-tumor therapy before. So far, 11 of planned 20 patients have been enrolled. Clinical trial information: NCT04181645 .

Download Full-text