Proof-of-concept study of Sym004, an anti-EGFR monoclonal antibody (mAb) mixture, in patients (pts) with anti-EGFR mab-refractory KRAS wild-type (wt) metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3551-3551 ◽  
Author(s):  
Rodrigo Dienstmann ◽  
Josep Tabernero ◽  
Eric Van Cutsem ◽  
Andres Cervantes-Ruiperez ◽  
Susana Rosello Keranen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mechanism Of Action ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Median Number ◽  
Clinical Activity ◽  
Tumor Shrinkage ◽  
Proof Of Concept ◽  
Open Label

3551 Background: KRAS wt mCRC pts progressing on chemotherapy and anti-EGFR mAbs have limited treatment options. Sym004 is a first-in-class drug mixture of two mAbs targeting non-overlapping epitopes on the EGFR, causing its internalization and degradation. With this unique mechanism of action, Sym004 overcomes acquired resistance to anti-EGFR mAbs in preclinical studies. Methods: Open-label, multicenter trial assessing safety (primary endpoint) and efficacy of 2 dose levels of Sym004 in KRAS wt mCRC pts with prior clinical benefit to anti-EGFR mAbs and subsequent progression during or within 6 months after treatment cessation. Sym004 was administered until disease progression or unacceptable toxicity. Tumor responses were evaluated centrally according to RECIST criteria. Paired skin and tumor biopsies were obtained at baseline and week 4. Results: In total, 42 pts were enrolled at 9 mg/kg (13) and 12 mg/kg (29). Median age was 66 years and median number of prior treatment lines 3. Central radiology review was performed in 12/13 (92%) pts at 9 mg/kg and 27/29 (93%) pts at 12 mg/kg. Tumor shrinkage > 10% was documented in 4/12 (33%) pts at 9 mg/kg, with partial response (PR) in 1/12 (8%) and stable disease (SD) in 9/12 (75%). At 12 mg/kg, 7/27 (26%) pts had > 10% tumor shrinkage, with PR in 3/27 (11%) and SD in 15/27 (56%). Median progression-free survival was 13.6 weeks (95% CI: 5.3-23) and 13.7 weeks (95% CI: 5.9-18.6), respectively. Duration of response for pts with PR was 5.6-17.6 weeks. Grade 3 or higher toxicity included skin rash in 26/42 (62%), hypomagnesemia in 16/42 (38%) and diarrhea in 2/42 (8%). Adverse events were manageable with dose reduction and supportive medication. There were no indications of immunogenicity. Pharmacodynamic analysis in serial tumor samples showed profound down-regulation of EGFR and reduction in proliferation marker Ki67. Conclusions: Sym004 at weekly doses of 9 and 12 mg/kg showed significant clinical activity in anti-EGFR treatment-refractory KRAS wt mCRC pts, clearly demonstrating proof-of-concept. Serial biopsies confirmed its mechanism of action. No unexpected adverse events were observed. Clinical trial information: NCT01117428.

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.

A phase 1b multicenter study of trifluridine/tipiracil (FTD/TPI) in combination with irinotecan (IRI) in patients (pts) with metastatic or unresectable gastric and gastroesophageal adenocarcinoma (mGEC) after at least one line of treatment with a fluoropyrimidine and platinum (FP) containing regimen.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16006-e16006
Author(s):  
Farshid Dayyani ◽  
Kit Wah Tam ◽  
Edward Jae-Hoon Kim ◽  
Samuel Ejadi ◽  
Fa Chyi Lee ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Open Label ◽  
Meaningful Improvement ◽  
Best Response ◽  
Previously Treated ◽  
Phase 1B

e16006 Background: FTD/TPI, an antimetabolite, is approved for treatment of refractory mGEC. This study sought to determine whether the combination of FTD/TPI with IRI (“TASIRI”) was safe and effective in mGEC previously treated with FP. Methods: This investigator‐initiated, multicenter, open‐label, single-dose level, single‐arm phase 1b study enrolled pts with mGEC previously treated with at least one line of FP containing regimen. FTD/TPI was given at 25 mg/m2 twice daily on days 1 to 5 with 180 mg/m2 IRI on day 1 of a 14‐day cycle. The primary endpoint was progression-free survival at six months (mo) (PFS-6). The aim was to show an improvement of PFS-6 from 15% to at least 30% based on historical controls. Results: At the time of data-cutoff (03Feb2021), 23 pts were screened and ultimately 20 pts were treated. The study met its primary endpoint. With a median follow-up of 9.8 mo (range 0.7 – 17), 8 pts are still on treatment and 4 pts have died. PFS-6 is 53.9% (lower limit of 95% CI: 28%). Median PFS and overall survival are 6.9 mo and not reached, respectively. At the time of data-cutoff, data were available for 13 pts with measurable disease by RECIST criteria and at least 1 on-treatment scan. Of those, 11 had stable disease and 2 had progressive disease as best response (5 pts had tumor shrinkage < 30%), therefore the disease control rate was 84.6%. The most common any grade (G) treatment related adverse events (TRAE) were nausea (n = 14, 70%), diarrhea (n = 9, 45%), and fatigue (n = 8, 40%). G3-4 TRAE in > 5% of pts were anemia (17%) and neutropenia (9%). 2 serious TRAE were reported: G4 febrile neutropenia (n = 1) and G3 hypotension (n = 1). There was no G5 TRAE. Conclusions: The combination of TASIRI showed encouraging clinical activity with a meaningful improvement in PFS-6 compared to historic controls. TASIRI was well tolerated and no new safety signals were seen. TASIRI warrants further investigation for patients with refractory mGEC and limited treatment options. Updated results with longer follow-up will be presented at the meeting. Clinical trial information: NCT04074343.

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]

Selinexor containing regimens in patients with multiple myeloma (MM) previously treated with anti-CD38 monoclonal antibodies (αCD38 mAbs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20020-e20020
Author(s):  
Cristina Gasparetto ◽  
Brea Lipe ◽  
Sascha Tuchman ◽  
Nizar J. Bahlis ◽  
Heather J. Sutherland ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Nuclear Export ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Median Number ◽  
Open Label ◽  
Previously Treated ◽  
Functional Inactivation ◽  
Dose Modifications

e20020 Background: Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins, is required for MM growth, is associated with poor prognosis in MM and mediates resistance to standard MM therapies. Selinexor (SEL) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound approved in combination with dexamethasone (dex) ± bortezomib for patients (pts) with previously treated MM. Once MM becomes refractory to αCD38 mAb, pts have limited effective treatment options and poor prognosis. Overall response rate (ORR) to the first regimen after refractoriness to an αCD38 mAb is 31%, median progression-free survival (mPFS) is 3.4 months (m), and median overall survival (mOS) is 8.6 m. The doublet SEL-dex (Xd) has shown ORR ̃26% in triple-class (IMID, PI, αCD38 mAb) refractory MM; SEL-based triplets could be more effective in this population. Methods: STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) is a multi-arm, open-label, Phase 1b/2 study evaluating SEL in various triplet combinations. Here, we retrospectively analyzed the efficacy and safety of SEL-containing triplets in pts previously treated with αCD38 mAbs. Pts received SEL-dex (Xd) plus pomalidomide (XPd, n = 19), bortezomib (XVd, n = 4), lenalidomide (XRd, n = 4), daratumumab (XDd, n = 2) or carfilzomib (XKd, n = 18). ORR, mOS, mPFS and adverse events (AEs) were analyzed. Results: Among the 47 pts, median age 64 yrs, female 53%, median time from diagnosis 5.1 yrs, median number of prior regimens 5 (range, 2–11). Prior daratumumab (96%), isatuximab (4%); 96% had MM refractory to aCD38 mAb, 81% had triple-class refractory MM, 74% and 47% were quad- and penta-exposed, 43% and 15% had quad- and penta-refractory MM. αCD38 mAb was included in the immediate prior regimen of 57% of pts and median duration from end of most recent aCD38 mAb therapy to first dose of study treatment was 6.9 weeks (range, 2.6-114.9). ORR was 51% among the 45 evaluable pts, 59% in the XPd arm (n = 17; 2 pts were not efficacy evaluable) and 67% in the XKd arm. ORR was 47% (9/19) among pts with quad-refractory MM and evaluable efficacy. Among all evaluable pts mPFS was 8.8 m (95% CI: 4.9, NE) and mOS was 20.4 m (95% CI: 9.6, NE). Among the 25 pts with αCD38 mAb in their immediate prior regimen, efficacy was similar to that regimen: ORR 52% vs. 45%, mPFS 8.8 vs. 9.3 m. The most common treatment emergent AEs were nausea (72%), anemia (64%), thrombocytopenia (60%), fatigue (57%), which were managed with standard supportive care and dose modifications. Conclusions: SEL-containing triplets in pts with MM previously treated with αCD38 mAbs, most of whom had triple-class refractory MM, exhibit tolerability and comparable effectiveness to their most recent αCD38 mAb-containing regimens. Compared to historical control, mOS was much higher among these patients. Further investigation is warranted. Clinical trial information: NCT02343042.

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.

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.

Phase IIa trial of cilengitide (EMD121974) single-agent therapy in patients (pts) with recurrent glioblastoma (GBM): EMD 121974-009

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2002-2002 ◽  
Author(s):  
D. Reardon ◽  
K. Fink ◽  
B. Nabors ◽  
T. Cloughesy ◽  
S. Plotkin ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Recurrent Glioblastoma ◽  
Tumor Control ◽  
Clinical Activity ◽  
Open Label ◽  
Recurrent Gbm

2002 Background: Our phase IIa study evaluated the safety, toxicity, and clinical activity of the cyclic RGD pentapeptide cilengitide (EMD121974), an inhibitor of integrins avβ3 and avβ5, as a single agent at doses of 500 and 2000 mg in pts with recurrent GBM. Methods: In this multicenter, open-label, randomized, uncontrolled study, pts with GBM and measurable disease that had relapsed after previous temozolomide and radiotherapy were randomized to receive cilengitide at either 500 mg or 2000 mg i.v., 2x/week, until progression. Neurologic exams were performed after every cycle (4 weeks) and MRIs were performed every other cycle. Central, blinded pathology and radiology reviews were performed. The primary endpoint was Progression Free Survival (PFS) at 6 months (6-mth PFS). Secondary endpoints included response, survival, time to disease progression, safety, tolerability and pharmacokinetics (PK). Results: 81 pts accrued (median Karnofsky Performance Status 80%; median age 57 yrs) at 15 sites including 41 at the 500 mg and 40 at the 2000 mg dose levels. Demographic and pretreatment variables were comparable between dose level cohorts. The median number of infusions was 16 [range, 4–179]. PK studies revealed significantly greater exposures among the 2000 mg cohort. Treatment related NCI CTC grade 3 adverse events (AEs) included elevated transaminases (at 500 mg), arthralgia/ myalgia (at 500 mg), and weight increase/ edema (at 2000 mg) in 1 patient, respectively. No grade 4 therapy related AEs were reported. One CTC grade 2 cerebral hemorrhage was reported in a pt at progression. The 6- mth PFS was 16.1% (n=13/81 pts). 10 pts (12.3 %, n=4 with 500 mg, n=6 with 2000 mg) received 12 or more cycles. Six pts (7.4%) remain progression-free and on treatment. Median Overall Survival (mOS) was 6.5 mths [95% CI: 5.2–9.3 mths] in the 500 mg arm and 9.9 mths [95% CI, 6.3–15.7 mths] in the 2000 mg arm. Although not statistically significant, there was a trend towards better tumor control in pts receiving 2000 mg 2x/week. Conclusions: Cilengitide was well tolerated and demonstrated single agent activity in recurrent GBM, with long term disease stabilization in a subset of pts. [Table: see text]

scholarly journals CMET-16. A PHASE II TRIAL OF BEVACIZUMAB IN PATIENTS WITH RECURRENT SOLID TUMOR BRAIN METASTASES WHO HAVE PROGRESSED FOLLOWING WHOLE BRAIN RADIATION THERAPY (WBRT): FINAL RESULTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi54-vi54
Author(s):  
Priya Kumthekar ◽  
Karan Dixit ◽  
Sean Grimm ◽  
Rimas Lukas ◽  
Margaret Schwartz ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Solid Tumor ◽  
Treatment Options ◽  
Thrombotic Event ◽  
Progression Free Survival ◽  
Response Duration ◽  
Response Assessment ◽  
Median Number ◽  
Open Label

Abstract BACKGROUND Brain metastases (BM) are the most common intracranial tumor with limited treatment options following the progression after WBRT. METHODS This open label phase 2 study for patients have progressed following WBRT enrolled participants who received bevacizumab 10 mg/kg intravenously every two weeks until CNS disease progression (one cycle=4 weeks). The primary endpoint was objective radiographic tumor response as defined by modified Response Assessment in Neuro-oncology (RANO) criteria. Secondary endpoints included safety, progression free survival (PFS), time to response, duration of response, overall survival (OS), and quality of life (QOL) as measured by FACT-G and FACT-Br. RESULTS A total of 27 patients were registered of which 24 were evaluable for ORR (3 came off study prior to first follow up MRI brain). Median age was 53 (range 27–73), median number of cycles was 5.5 (range 1–20) with a median follow up of 8.7 months (range 2.4–47.9mo). Of the 24 evaluable patients, 6 showed radiographic response (Partial response=6, stable disease=16, progressive disease=2, 81% (22/24) experienced clinical benefit). The 6 month PFS: 46% (95% CI: 25% - 67%) and median PFS was 5.3 months. Median OS was 9.5 months (95% confidence interval 6.3m – 15.0m). For the patients who completed sequential QOL assessments, there no decline in QOL seen secondary to treatment and there was a non statistically significant improvement seen in the FACT-Br questionnaire. Overall, treatment was well tolerated with 3 grade 3 adverse events seen: hypertension (n=3), headache (n=1) and thrombotic event (n=1). CONCLUSION For this pretreated BM population with historically poor clinical outcome and survival, we showed disease response with bevacizumab therapy, drug tolerability and improved survival as compared to historical controls. While larger studies are needed to confirm, bevacizumab therapy could be a viable option for solid tumor BM patients who experience progression following WBRT.

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