Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 354-354 ◽  
Author(s):  
Scott T. Tagawa ◽  
Bishoy Morris Faltas ◽  
Elaine Tat Lam ◽  
Philip James Saylor ◽  
Aditya Bardia ◽  
...  
Keyword(s):  
Phase I ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Complete Response ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Metastatic Urothelial Cancer

354 Background: Patients (pts) with mUC who progress after platinum (PLT)-based chemotherapy and immune checkpoint inhibitor (CPI) therapy have poor outcomes and limited treatment options. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate. It consists of a monoclonal antibody targeting Trop-2, an epithelial cell surface antigen overexpressed in UC, conjugated to the active metabolite of irinotecan (SN38). Methods: We performed a phase I/II basket study in pts with advanced solid tumors receiving intravenous SG administered on day 1 and 8 of 21-day cycles, until progression or unacceptable toxicity. CT/MRI scans were obtained at 8-week intervals for response assessment. We evaluated pts with mUC who progressed after ≥1 prior systemic therapy and were treated with SG at the 10 mg/kg dose level. Endpoints included safety, objective response rate (ORR) by RECIST 1.1, clinical benefit rate (CBR; complete response [CR], partial response [PR], or else SD ≥6-mo), and Kaplan-Meier estimated duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: 45 pts (41M/4F; median age 67, range 49-90; ECOG 0/1: 31%/69%) received a median of 2 (range: 1-6) prior treatment lines, including PLT-based chemotherapy (95%) and CPI (38%). 33 had visceral metastases involving liver (n=15), lung (n=27), and other organs (n=5). The ORR was 31% (14/45), with 2 CR and 12 PR. In pts with visceral involvement, the ORR was 27% (9/33). The ORR in CPI-treated pts was 23% (4/17). The median DOR was 12.6 mo (2 pts continuing >2 y), and the CBR was 47% (21/45). Median PFS and OS were 7.3 mo and 18.9 mo, respectively. The AE profile was consistent with prior reports. Grade ≥3 AEs in ≥5% of pts were neutropenia/neutrophil count decreased (38%), anemia (11%), hypophosphatemia (11%), diarrhea (9%), fatigue (9%), and febrile neutropenia (7%). Conclusions: SG demonstrated clinical activity in pts with relapsed/refractory mUC, including CPI-treated pts and pts with visceral disease. A single-arm, open-label, global phase 2 trial is underway to evaluate antitumor activity and safety of SG in advanced UC.(TROPHY-U-01; NCT03547973). Clinical trial information: NCT03547973.

Sacituzumab govitecan (SG) in patients (pts) with previously treated metastatic endometrial cancer (mEC): results from a phase I/II study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6081-6081
Author(s):  
Alessandro Santin ◽  
Takefumi Komiya ◽  
David M. Goldenberg ◽  
Robert M. Sharkey ◽  
Quan Hong ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Bystander Effect ◽  
Clinical Investigation ◽  
Treatment Options ◽  
Objective Response ◽  
Surface Glycoprotein ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Cell Surface Glycoprotein

6081 Background: Unselected pts with EC who progressed on prior chemotherapy have a poor prognosis with limited treatment options. SG is a novel antibody-drug conjugate that targets Trop-2, a cell surface glycoprotein highly expressed in many epithelial tumors. It is conjugated to deliver SN-38, the active metabolite of irinotecan, via a proprietary hydrolyzable linker. Preclinical studies show SG has activity against chemotherapy-resistant EC and significant bystander effect against EC with heterogenous Trop-2 expression (Perrone E. Mol Oncol. 2019). Methods: The phase I/II basket study (NCT01631552) evaluated pts unselected for Trop-2 with advanced solid tumors who received intravenous SG (days 1 and 8 of 21-day cycles), until progression or unacceptable toxicity. CT/MRI scans were obtained at 8-week intervals for response assessment by RECIST 1.1. We report results for mEC pts who progressed after ≥1 prior systemic therapy and were treated with SG 10 mg/kg. Endpoints include safety, objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: 18 mEC pts (all women; 17 white and 1 black; median age 69 years [range, 41–76]) had a median 3.5 (range 2–6) prior lines of therapy. All pts received prior treatment with platinum therapies. At a median follow-up of 12.7 months, the ORR (95% CI) was 22.2% (6.4–47.6), with 4 partial responses. CBR (95% CI) was 44.4% (21.5–69.2), with 8 of 18 pts having either an objective response or stable disease ≥6 months. The DOR of responders ranged from 9.1 to 26.6 months, with 2 of 4 responders having a duration of ≥18 months. Median PFS (95% CI) was 3.2 months (1.9–9.4), and median OS (95% CI) was 11.9 months (4.7–not calculable). Key grade ≥3 TRAEs in the overall basket study safety population (n=495) included neutropenia (28%), neutrophil count decrease (14%), anemia (10%), diarrhea (8%), fatigue (6%), and febrile neutropenia (5%). A similar safety profile was seen in the mEC cohort. Conclusions: Median OS in unselected pts with mEC who progressed on prior platinum therapy is ~10 months with an ORR of ~10%. SG monotherapy showed clinical activity in pts with relapsed/refractory mEC, consistent with previous preclinical findings, and support further clinical investigation (NCT04251416). The phase II TROPiCS-03 (NCT03964727) study in pts with metastatic solid tumors selected based on elevated Trop-2 expression by a validated IHC assay will also provide further insights. Clinical trial information: NCT01631552.

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9504-9504 ◽  
Author(s):  
Egbert F. Smit ◽  
Kazuhiko Nakagawa ◽  
Misako Nagasaka ◽  
Enriqueta Felip ◽  
Yasushi Goto ◽  
...  
Keyword(s):  
Topoisomerase I ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Ecog Performance Status ◽  
Platinum Based Chemotherapy ◽  
Grade 3

9504 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and topoisomerase I inhibitor payload. In a phase I trial, patients (pts) with HER2-mutated NSCLC who received T-DXd had a confirmed objective response rate (ORR) of 72.7% (8/11) (Tsurutani et al, WCLC 2018). DESTINY-Lung01 (NCT03505710) is an ongoing, multicenter, phase II study of T-DXd in pts with non-squamous NSCLC overexpressing HER2 or containing a HER2-activating mutation. We report data for the cohort with HER2 mutations after a median follow-up of 8.0 mo (range, 1.4-14.2 mo). Methods: Pts were treated with T-DXd 6.4 mg/kg every 3 weeks. The primary endpoint was confirmed ORR (complete response [CR] + partial response [PR]) by ICR. Additional endpoints were disease control rate (DCR; CR + PR + stable disease), duration of response (DOR), progression-free survival (PFS), and safety. Results: At data cutoff (25 Nov 2019), 42 pts (64.3% female) had received T-DXd. Median age was 63.0 years (range, 34-83 years; < 65 y, 59.5%); 45.2% had central nervous system metastases; ECOG performance status was 0 in 23.8% of pts and 1 in 76.2%. HER2 mutations were predominantly in the kinase domain (90.5%). Most pts (90.5%) had prior platinum-based chemotherapy and 54.8% had anti–PD-1 or –PD-L1 treatment; median number of prior treatment lines was 2 (range, 1-6). Median treatment duration was 7.75 mo (range, 0.7-14.3 mo); 45.2% of pts remained on treatment. Confirmed ORR by ICR among the 42 pts was 61.9% (95% CI, 45.6%-76.4%); median DOR was not reached at data cutoff; 16 of 26 responders remained on treatment at data cutoff; DCR was 90.5% (95% CI, 77.4%-97.3%); estimated median PFS was 14.0 mo (95% CI, 6.4-14.0 mo). All pts (42/42) had treatment-emergent adverse events (TEAEs); 64.3% were grade ≥ 3 (52.4% drug-related), including decreased neutrophil count (26.2%) and anemia (16.7%). There were 5 cases (11.9%) of drug-related interstitial lung disease (ILD) as adjudicated by an independent committee (all grade 2, no grade ≥ 3) and 1 case of grade 1 ILD is pending adjudication. TEAEs led to dose interruption in 25 pts (59.5%), dose reduction in 16 pts (38.1%), and treatment discontinuation in 10 pts (23.8%). Conclusions: T-DXd demonstrated promising clinical activity with high ORR and durable responses in pts with HER2-mutated NSCLC. The safety profile was generally consistent with previously reported studies. Clinical trial information: NCT03505710 .

An open-label, multicohort, phase I/II study of nivolumab in patients with virus-associated tumors (CheckMate 358): Efficacy and safety in recurrent or metastatic (R/M) cervical, vaginal, and vulvar cancers.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5504-5504 ◽  
Author(s):  
Antoine Hollebecque ◽  
Tim Meyer ◽  
Kathleen N. Moore ◽  
Jean-Pascal H. Machiels ◽  
Jacques De Greve ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hpv Infection ◽  
Clinical Activity ◽  
Open Label ◽  
First Line Therapy ◽  
Hpv Status ◽  
Ecog Ps

5504 Background: Treatment options for cervical, vaginal, and vulvar (GYN) cancers are limited after first-line therapy. Human papillomavirus (HPV) infection is associated with squamous cell carcinomas of the cervix (≥90%) and vulva/vagina (40–70%), and may elicit an immune reaction. Programmed death (PD)-1 and its major ligand PD-L1 are expressed in GYN cancers and inhibit immune responses. Nivolumab disrupts PD-1–mediated signaling, restoring antitumor immunity. Methods: In CheckMate 358 (NCT02488759), an ongoing multicohort study of 5 virus-associated cancers, PD-L1–unselected adults with R/M GYN cancers, ECOG PS 0–1, and ≤2 prior systemic therapies for R/M disease were eligible to receive nivolumab 240 mg every 2 weeks until progression or unacceptable toxicity. Primary endpoints were objective response rate (ORR) and safety; secondary endpoints were duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: Of 24 treated patients (pts), 19 had cervical and 5 had vaginal or vulvar cancer; median age was 51 y. At a median follow-up of 31 wks (range: 6–38), ORR was 20.8% (Table), and disease control rate (ORR + SD) was 70.8%. All responses were in pts with cervical cancer (ORR, 26.3%) and were observed regardless of PD-L1 or HPV status or number of prior R/M therapies. Median PFS was 5.5 mo (95% CI: 3.5, NR); median OS was NR. Conclusions: Nivolumab demonstrated encouraging clinical activity in pts with cervical cancer and a manageable safety profile in virus-associated GYN cancers, supporting further evaluation in these pts. Updated clinical and biomarker data to be presented. Clinical trial information: NCT02488759. [Table: see text]

scholarly journals 357 Toripalimab plus chemoradiotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase II trial

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A384-A384
Author(s):  
Xiaoting Xu ◽  
Jian Huan ◽  
Hui Miao ◽  
Hao Wang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Treatment Options ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Nccn Guidelines ◽  
Significant Difference ◽  
Grade 3

BackgroundRecurrent or metastatic cervical cancer patients who progressed after standard therapy have limited treatment options and poor prognosis with a 1-year survival rate ranging between 15% and 20%. This study evaluates the efficacy and safety of toripalimab plus chemoradiotherapy in patients with recurrent or metastatic cervical cancer (Clinical trial ID: ChiCTR2000029068)MethodsIn this open-label, single-arm, phase 2 study conducted at four radiotherapy centers in East China, eligible patients were confirmed by pathology and/or imaging for recurrent or metastatic cervical cancer. According to the first-line therapies for cervical cancer recommended by NCCN guidelines, all patients were received paclitaxel plus cisplatin regimen, with or without bevacizumab, combined with radiotherapy. After seven fractions radiotherapy at the recurrent or metastatic regions, 240 mg toripalimab every three weeks for six cycles or more were given in combination.ResultsBetween Jan 14th, 2020, and May 1st, 2021, 24 patients were enrolled. All patients were staged at the first visit, as seven patients were with FIGO (2018) stage I, 10 with stage II, 2 with stage III, 1 with stage IV, and 2 with unclear stage. Of 24 included patients, 22 (91.67%) had squamous cervical cancer. The median age was 55 (range, 33–72) years. As of May 31, 2021, median follow-up time was 8.5 months [95% CI: 2.3–10.1]. 14 (58.3%) of 24 patients who achieved an objective response, including 10 (41.7%) complete response (CR) and 4 (16.7%) partial response (PR). The median duration of response was not reached and 7 (29.1%) patients continued toripalimab treatment after the previous 6-cycle immunotherapy. The disease control rate was 75% (18/24). Median progression-free survival (PFS) was 8.61 months (95% CI: 4.14–not reached). For subgroup analysis, the median PFS was significantly prolonged in the CR/PR group compared with that in the SD/PD group [not reached (95% CI: 6.21–not reached) versus 5.5 months (95% CI: 2.69–6.870), P = 0.023]. There was no significant difference in the median PFS between patients who previously received radiotherapy (8.61 months) and those who didn’t (6.87 months) (P = 0.641). 8 (33.3%) patients had grade 3–4 treatment-related adverse events (TRAEs). The most common grade 3-4 TRAEs were myelosuppression (29.2%), hypertriglyceridemia (8.3%), hypoalbuminemia (4.2%), pneumonia (4.2%), and hypercholesterolemia (4.2%).ConclusionsToripalimab plus chemoradiotherapy showed promising antitumor activity and tolerable toxicities in patients with recurrent or metastatic cervical cancer.

Safety and activity of nivolumab monotherapy in advanced and metastatic (A/M) gastric or gastroesophageal junction cancer (GC/GEC): Results from the CheckMate-032 study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 6-6 ◽  
Author(s):  
Dung T. Le ◽  
Johanna C. Bendell ◽  
Emiliano Calvo ◽  
Joseph W. Kim ◽  
Paolo Antonio Ascierto ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Gastroesophageal Junction Cancer ◽  
Duration Of Response

6 Background: Patients (pts) with GC/GEC often present with A/M disease, which has a poor prognosis, with 1-year survival < 30%, and few treatment options. Nivolumab is a fully human anti-PD-1 IgG4 monoclonal antibody with a favorable safety profile and efficacy in melanoma, non–small-cell lung cancer, and renal cell carcinoma. The phase I/II, open-label CheckMate-032 study evaluated nivolumab ± ipilimumab in pts with solid tumors. Here, we report initial results for pts with GEC/GC receiving nivolumab monotherapy. Methods: Pts with A/M histologically confirmed GC/GEC, irrespective of PD-L1 status, were assigned to receive nivolumab alone (3 mg/kg IV Q2W) and treated until disease progression (PD) or intolerable toxicity. The primary endpoint was objective response rate (ORR); other endpoints included safety, progression-free survival, overall survival (OS), and biomarker status. Results: 59 pts were enrolled and treated with single-agent nivolumab. Median age was 60 y (range 29–80), and 83% of pts received ≥ 2 prior regimens. At database lock, 10 pts were on active treatment; 49 pts discontinued (PD, n = 40; unrelated adverse events, n = 4; treatment-related adverse events [TRAEs], n = 2; other, n = 3). Pts received a median of 4 doses (range 1–25). ORR was 12% (n = 7/58; 1 complete response, 6 partial responses); 12 pts (21%) had stable disease. Among responders, median duration of response was 7.1 mo (95% CI, 3.0–13.2). Median OS was 6.8 mo (95% CI, 3.3–12.4); 12-mo OS rate was 38% (95% CI, 23.2–52.7). 39% of tumor samples were PD-L1 positive ( ≥ 1% cutoff). ORRs in pts with PD-L1-positive and -negative tumors were 18% and 12%, respectively. TRAEs occurred in 66% of pts; most were Grade 1/2. Grade 3/4 TRAEs occurred in 14% of pts and included pneumonitis, fatigue, diarrhea, vomiting, hypothyroidism, and increased aspartate and alanine aminotransferase and alkaline phosphatase levels. No treatment-related deaths occurred. Conclusions: Nivolumab monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated pts with GC/GEC. Objective responses occurred in pts with PD-L1-positive and -negative tumors. Clinical trial information: NCT01928394.

An open-label, multicohort, phase I/II study to evaluate nivolumab in patients with virus-associated tumors (CheckMate 358): Efficacy and safety in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6025-6025 ◽  
Author(s):  
Jean-Pierre Delord ◽  
Antoine Hollebecque ◽  
J. P. De Boer ◽  
Jacques De Greve ◽  
Jean-Pascal H. Machiels ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Immune Recognition ◽  
Open Label ◽  
Ongoing Research ◽  
Barr Virus ◽  
Epstein Barr ◽  
Ecog Ps

6025 Background: Treatment options for patients (pts) with R/M NPC are limited to palliative chemotherapy. NPC is often associated with the Epstein–Barr virus (EBV), a potential antigen for immune recognition, and high expression levels of the immune checkpoint receptor programmed death-1 (PD-1) and its major ligand PD-L1. Nivolumab disrupts PD-1–mediated signaling, restoring T-cell antitumor function. Methods: In CheckMate 358 (NCT02488759), PD-L1–unselected adults with R/M NPC, ECOG PS of 0–1, and ≤2 prior systemic therapies in the R/M setting were eligible to receive nivolumab 240 mg every 2 weeks until progression or unacceptable toxicity, as part of an ongoing multicohort study of 5 virus-associated cancers. Human papillomavirus-associated NPC and keratinizing squamous cell carcinoma (WHO Type 1) were excluded. Primary endpoints were objective response rate (ORR) and safety; secondary endpoints were duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: Of 24 treated pts with R/M NPC, median age was 51 years, 88% were male, 62% were white, 88% were European, and 88% had EBV+ tumors. At a median follow-up of 26 weeks (range: 4–40), ORR was 20.8% and appeared to be higher in pts with no prior R/M therapy (Table). The disease control rate (ORR + SD) was 45.8%. Responses were observed regardless of PD-L1 or EBV status. Median PFS was 2.4 mo (95% CI: 1.5, NR); median OS was NR. Conclusions: Nivolumab demonstrated clinical activity and a manageable safety profile in R/M NPC, supporting ongoing research with nivolumab in this disease. Updated efficacy and biomarker data will be presented. Clinical trial information: NCT02488759. [Table: see text]

FRACTION (Fast Real-time Assessment of Combination Therapies in Immuno-Oncology)-gastric cancer (GC): A randomized, open-label, adaptive, phase 2 study of nivolumab in combination with other immuno-oncology (IO) agents in patients with advanced GC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4137-TPS4137 ◽  
Author(s):  
Praveen Aanur ◽  
Martin Gutierrez ◽  
Ronan Joseph Kelly ◽  
Jaffer A. Ajani ◽  
Geoffrey Yuyat Ku ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rapid Development ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
New Combination ◽  
Clinical Activity ◽  
Phase 2 ◽  
Open Label

TPS4137 Background: Nivolumab, a fully human IgG4 mAb that targets programmed death-1, alone and in combination with ipilimumab, a fully human IgG1 mAb that targets cytotoxic T-lymphocyte antigen 4, has demonstrated encouraging clinical activity in patients with advanced GC. These data support the rationale that nivolumab in combination with other IO agents or targeted therapies may improve treatment outcomes in patients with advanced GC. Given the rapid development of novel IO agents, traditional studies cannot efficiently evaluate all possible IO-IO and IO-targeted therapy combinations. FRACTION is an innovative clinical trial program with a rolling, adaptive platform design that allows for the addition of new combination regimens, as well as withdrawal of ineffective regimens. Here we describe the study concept, key design components, and the first IO treatment combinations of FRACTION-GC, a phase 2, randomized, open-label, adaptive study in advanced GC (NCT02935634). Methods: Patients with advanced GC or gastroesophageal junction (GEJ) cancer will be enrolled based on prior IO treatment and randomized to receive nivolumab plus BMS-986016 (fully human IgG4 mAb that targets lymphocyte activation gene 3) or nivolumab plus ipilimumab. Enrollment is continuous and may offer patients consecutive treatment options based on their treatment exposure and response. The primary endpoints are objective response rate, duration of response, and progression-free survival rate at 24 weeks. The secondary endpoint is safety. Comprehensive biomarker analyses will also be performed. New treatment combinations will be added over time to explore their potential benefits and to provide a continuous flow of treatment options for patients whose cancer progresses on existing treatments. In this way, FRACTION-GC is envisioned to accelerate the development of the next generation of IO combinations for patients with metastatic GC and GEJ cancer. Clinical trial information: NCT02935634.

Final results of a phase II trial of first-line FOLFIRINOX for advanced gastroesophageal cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4532-4532
Author(s):  
Ramon Jin ◽  
Haeseong Park ◽  
Andrea Wang-Gillam ◽  
Rama Suresh ◽  
Caron E. Rigden ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
First Line ◽  
Her2 Positive ◽  
Open Label

4532 Background: Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have moderate clinical benefit with objective response rates (ORR) of approximately 40-50%. FOLFIRINOX has been shown to be an effective and well-tolerated first line therapy in other GI cancers. In this open-label, single-arm phase II study of patients with advanced gastroesophageal adenocarcinomas, we sought to evaluate the safety and clinical activity of FOLFIRINOX. Methods: The primary endpoint was ORR, and secondary endpoints included safety profile, progression free survival (PFS), overall survival (OS), time to progression (TTP), clinical benefit rate (CBR), and duration of response. Estimated sample size included 41 patients with HER2 negative disease with 90% power to detect an ORR≥60% with alpha of 0.10. No enrollment goal was planned for HER2 positive patients, but they were allowed participation to receive study treatment in combination with trastuzumab. Treatment consisted of 400mg/m2 5-FU bolus, 400 mg/m2 leucovorin, 2400 mg/m2 5-FU infusion over 46 hours, 180 mg/m2 irinotecan, and 85 mg/m2 oxaliplatin. Trastuzumab was administered intravenously as a 6 mg/kg loading dose then given 4 mg/kg every 14 days for HER2 positive patients. This trial is registered with ClinicalTrials.gov, NCT01928290. Results: From November 2013 to May 2019, 67 patients were enrolled, of which 26 (39%) had HER2 positive disease. Median follow-up was 16.1 months. ORR was 61% (25/41) for HER2 negative and 85% (22/26) for HER2 positive groups. Overall, one patient (2%) had a complete response, 36 patients (69%) had partial responses, and 13 patients (19%) had stable disease for >6 months; therefore, CBR was 96%. Median PFS was 11.9 months, median OS was 17.4 months. 41 patients (83.7%) had dose modification or treatment delay with the most common toxicities being neutropenia, diarrhea, peripheral sensory neuropathy, and nausea with no unexpected toxicities. Conclusions: FOLFIRINOX is a highly effective three-drug regimen for first-line treatment of advanced gastroesophageal cancer with expected, tolerable toxicities. Clinical trial information: NCT01928290 .

Updated results of a phase IIa study to evaluate the clinical efficacy and safety of erdafitinib in Asian advanced cholangiocarcinoma (CCA) patients with FGFR alterations.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4117-4117 ◽  
Author(s):  
Joon Oh Park ◽  
Yin-Hsun Feng ◽  
Yen-Yang Chen ◽  
Wu-Chou Su ◽  
Do-Youn Oh ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Treatment Options ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Median Number ◽  
Clinical Activity ◽  
Open Label ◽  
Orally Bioavailable ◽  
Tumor Types

4117 Background: Patients (pts) with advanced CCA who progressed on or after first line chemotherapy have no approved treatment options. Fibroblast growth factor receptor (FGFR) gene alterations are observed in many tumor types including 14-17% in CCA. Erdafitinib, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown clinical activity against solid tumors with FGFR alterations. Methods: LUC2001 is an open-label, multicenter, Ph2a study in advanced CCA pts with FGFR alterations (FoundationOne), who progressed after ≥ 1 prior treatment. The primary endpoint is objective response rate (ORR; RECIST 1.1). The secondary endpoints are disease control rate (DCR), progression free survival (PFS), duration of response (DOR), safety and pharmacokinetics (PK). Disease is evaluated every 8 weeks until disease progression (PD). Results: As of 3 Dec 2018, 222 CCA pts were molecularly screened; 34 had FGFR alterations, of whom 14 (8 FGFR2 fusion, 3 FGFR2 mutation, 1 FGFR3 fusion, 2 FGFR3 mutation) were dosed 8 mg once daily with up titration option. Median age was 51.5 years. 13/14 and 12/14 pts had prior platinum or gemcitabine based therapy respectively, 7/14 pts got re-treated with platinum or gemcitabine based therapy, and 9/14 pts had ≥2 prior lines of therapy. Median number of treatment cycles was 5.0 (range: 1; 22) and treatment duration was 4.83 (range: 0.5; 20.3) months. In 12 evaluable pts, there were 6 confirmed partial response (PR), 4 stable disease (SD) and 2 PD; ORR (CR+PR) was 6/12 (50.0%), DCR (CR+PR+uCR+uPR+SD) was 10/12 (83.3%); median DOR was 6.83 months (95% CI: 3.65; 12.16); median PFS was 5.59 months (95% CI: 1.87, 13.67). In 10 evaluable FGFR2+ pts, ORR was 6/10 (60.0%); DCR was 10/10(100%); median PFS was 12.35 months (95% CI: 3.15, 19.38). The most common TEAEs ( > 30%) were hyperphosphatemia, dry mouth, stomatitis, and dry skin. 9 pts had ≥ Grade 3 AEs (8 Grade 3,1 Grade 5), of which 7 drug related. TEAE led to treatment 1 discontinuation, 6 dose reductions and 1 death (not drug related). The results of PK and PK/PD relationship were consistent with other erdafitinib studies in different ethnic background pts. Conclusions: Asian advanced CCA pts with FGFR alterations treated with erdafitinib had encouraging efficacy and acceptable safety profile similar to experience in other tumor types and populations. Clinical trial information: NCT02699606.

Avelumab treatment for metastatic urothelial carcinoma in the phase Ib JAVELIN Solid Tumor Study: Updated safety and efficacy analysis with ≥ two years of follow-up.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 425-425 ◽  
Author(s):  
Andrea B. Apolo ◽  
John Allan Ellerton ◽  
Jeffrey R. Infante ◽  
Manish Agrawal ◽  
Michael S. Gordon ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Pooled Analysis ◽  
Clinical Activity ◽  
Efficacy Analysis ◽  
Tumor Study ◽  
Metastatic Urothelial Cancer ◽  
Duration Of Response

425 Background: Avelumab, a human anti‒PD-L1 IgG1 antibody, is approved for the treatment of metastatic urothelial cancer (mUC) progressing after platinum chemotherapy in the US, Canada, and Israel. Here, we report an updated pooled analysis of 2 cohorts of avelumab-treated patients (pts) with mUC from the JAVELIN Solid Tumor study (NCT01772004). Methods: Pts with mUC whose disease had progressed after platinum-based therapy or were cisplatin ineligible received avelumab 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by independent review (RECIST v1.1). Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (NCI CTCAE v4.0). Results: As of April 2018, 249 pts had received avelumab and had been followed for ≥2 years (median 2.7 years). Median treatment duration was 12.0 weeks (IQR, 6.0-32.1), and 12 pts (4.8%) remained on treatment. Confirmed ORR in all evaluable pts (n = 242) was 16.5% (95% CI: 12.1%-21.8%; complete response in 4.1%). Median DOR was 20.5 mo (95% CI: 9.7-not estimable), and the Kaplan-Meier (K-M) estimate of 12-mo DOR was 65.4% (95% CI: 47.0%-78.8%). Median PFS was 1.6 mo (95% CI: 1.4-2.7 mo), median OS was 7.0 mo (95% CI: 5.9-8.5 mo), and the K-M 12-mo and 24-mo OS rates were 35.9% (95% CI: 29.9%-42.0%) and 20.1% (95% CI: 15.2%-25.4%), respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 71.1% of pts (177/249), most commonly infusion-related reactions (24.1%), fatigue (18.1%) and rash (18.1%). Grade ≥3 TRAEs occurred in 11.6% of pts (29/249), most commonly fatigue (1.6%), elevated lipase (1.6%), and pneumonitis (1.2%). Ten pts (4.0%) discontinued avelumab due to a TRAE. There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab showed durable clinical activity and had a manageable safety profile in pts with mUC. A phase 3 trial of avelumab in the maintenance setting after first-line platinum-based therapy for mUC is ongoing. Clinical trial information: NCT01772004.

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