Enfortumab vedotin (EV) in patients (Pts) with metastatic urothelial carcinoma (mUC) with prior checkpoint inhibitor (CPI) failure: A prospective cohort of an ongoing phase 1 study.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 431-431 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
David C. Smith ◽  
Thomas W. Flaig ◽  
Jingsong Zhang ◽  
Srikala S. Sridhar ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Disease Progression ◽  
Phase 1 ◽  
Unmet Need ◽  
Phase 2 ◽  
Phase 1 Study ◽  
Primary Tumor Site ◽  
Metastatic Setting ◽  
Almost All ◽  
Ongoing Phase

431 Background: EV is an ADC that selectively targets and kills cells expressing Nectin-4 by delivering a potent microtubule-disrupting agent, monomethyl auristatin E. As mUC tumors express Nectin-4 in almost all pts, the EV clinical profile was assessed in an ongoing Phase 1 study (NCT02091999) at the recommended phase 2 dose (RP2D; 1.25 mg/kg) in mUC pts with CPI failure, a population with a high unmet medical need. Methods: Pts with mUC, treated with ≥1 prior chemotherapy or who were ineligible for platinum chemotherapy, and who had disease progression after CPI therapy received an IV infusion of EV at RP2D on Days 1, 8, and 15 of each 28-day cycle. Primary endpoint was tolerability; a secondary endpoint was investigator-assessed antitumor activity per RECIST v1.1. Results: As of 2 Oct 2017, 62 pts with mUC and prior CPI failure received EV at RP2D (48 M/14 F; median age, 68 yr [range: 41–83]; ECOG 0/1 29%/71%). Primary tumor site was bladder in 73% pts; 63% pts had visceral and 27% had liver metastasis (LM). Most pts (71%) had ≥2 prior therapies in the metastatic setting, including platinum (87%) or taxanes (26%). CPI was the most recent therapy in 76% pts; time from last CPI to first EV dose was < 12 wk for 58% pts. Median treatment duration was 14.8 wk (range: 1.6–40.4); 39 pts continue treatment. Treatment-related AEs occurring in ≥30% pts were fatigue, rash, nausea, alopecia, decreased appetite and diarrhea; most grade ≤2. Grade ≥3 AE reported in ≥5% pts, regardless of attribution, was hyponatremia (6.5%). One fatal AE (respiratory failure) was possibly treatment related. Response evaluable pts (n = 54) had ≥1 post baseline scan or discontinued prior to scan. ORR (confirmed + unconfirmed) was 54% (95% CI: 39.6–67.4); 15 pts had a confirmed PR, 5 had unconfirmed PR, and 9 are pending subsequent assessment. This ORR is similar to CPI-naïve pts (59%; 95% CI: 36.4–79.3). ORR from 17 evaluable pts with LM was 41% (95% CI: 18.4–67.1). Conclusions: EV is tolerable and exhibits antitumor activity in a cohort of pts with mUC and disease progression after CPI. A phase 2 study assessing EV in this population with high unmet need has been initiated (NCT03219333; EV-201 study). Clinical trial information: NCT02091999.

Antitumor activity of ASP8273 300 mg in subjects with EGFR mutation-positive non-small cell lung cancer: Interim results from an ongoing phase 1 study.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 9050-9050 ◽  
Author(s):  
Helena Alexandra Yu ◽  
Alexander I. Spira ◽  
Leora Horn ◽  
Jared Weiss ◽  
Howard Jack West ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Phase 1 ◽  
Small Cell ◽  
Small Cell Lung ◽  
Phase 1 Study ◽  
Ongoing Phase

scholarly journals Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study

2020 ◽  
Vol 8 (1) ◽  
pp. e000437
Author(s):  
Lin Shen ◽  
Jun Guo ◽  
Qingyuan Zhang ◽  
Hongming Pan ◽  
Ying Yuan ◽  
...  
Keyword(s):  
Cell Death ◽  
Antitumor Activity ◽  
Programmed Cell Death ◽  
Solid Tumors ◽  
Phase 1 ◽  
Chinese Patients ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
Dose Verification ◽  
Open Label

BackgroundTislelizumab is an investigational, humanized, IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death-1 (PD-1) that was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy.MethodsThe purpose of this phase 1/2, open-label, non-comparative study was to examine the safety, tolerability, and antitumor activity of tislelizumab in adult (≥18 years) Chinese patients with histologically or cytologically confirmed advanced solid tumors with measurable disease. The phase 1 portion of the study consisted of a dose-verification study and a pharmacokinetic (PK) substudy; phase 2 was an indication-expansion study including 11 solid tumor cohorts. Patients previously treated with therapies targeting PD-1 or its ligand, programmed cell death ligand-1 were excluded. During dose-verification, dose-limiting toxicities (DLTs) were monitored; safety and tolerability were examined and the previously determined recommended phase 2 dose (RP2D) was verified. The primary endpoint of phase 2 was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors V.1.1.ResultsAs of December 1, 2018, 300 patients were treated with tislelizumab 200 mg intravenously once every 3 weeks (Q3W). Median duration of follow-up was 8.1 months (range 0.2–21.9). No DLTs were reported during the phase 1 dose-verification study and the RP2D was confirmed to be 200 mg intravenously Q3W. Most treatment-related adverse events (62%) were grade 1 or 2, with the most common being anemia (n=70; 23%) and increased aspartate aminotransferase (n=67; 22%). Of the 251 efficacy evaluable patients, 45 (18%) achieved a confirmed clinical response, including one patient from the PK substudy who achieved a complete response. Median duration of response was not reached for all except the nasopharyngeal carcinoma cohort (8.3 months). Antitumor responses were observed in multiple tumor types.ConclusionsTislelizumab was generally well tolerated among Chinese patients. Antitumor activity was observed in patients with multiple solid tumors.Trial registration numberCTR20160872.

scholarly journals A phase 1 study of azacitidine with high-dose cytarabine and mitoxantrone in high-risk acute myeloid leukemia

2020 ◽  
Vol 4 (4) ◽  
pp. 599-606 ◽  
Author(s):  
Kirk E. Cahill ◽  
Yasmin H. Karimi ◽  
Theodore G. Karrison ◽  
Nitin Jain ◽  
Margaret Green ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Phase 1 ◽  
High Dose ◽  
Phase 2 ◽  
Phase 1 Study ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Abstract In this phase 1 study, azacitidine (AZA) was given before high-dose cytarabine (HiDAC) and mitoxantrone (mito) based on the hypothesis that epigenetic priming with a hypomethylating agent before cytotoxic chemotherapy would improve response rates in patients with high-risk acute myeloid leukemia (AML), including relapsed/refractory disease. The primary objective was to establish the recommended phase 2 dose of AZA given before standard HiDAC/mito. In a dose escalation scheme, 46 patients (median age, 66 years) received AZA at 37.5, 50, or 75 mg/m2 subcutaneously or IV once daily on days 1 to 5 followed by HiDAC (3000 mg/m2) and mitoxantrone (30 mg/m2) once each on days 6 and 10 (the HiDAC/mito dose was reduced 33% in elderly subjects). Two dose-limiting toxicities occurred (both in the same patient): acute liver failure and kidney injury at the 50 mg/m2 dose. The 30-day induction death rate was 2.2% (1 of 46). The overall response rate, including complete remission and complete remission with incomplete count recovery, was 61% (28 of 46). Previously untreated patients aged ≥60 years with therapy-related AML and de novo AML were more likely to respond than untreated patients with AML progressing from an antecedent hematologic disorder (myelodysplastic syndrome and chronic myelomonocytic leukemia). Patients with favorable European Leukemia Network risk (P = .008), NPM1 mutations (P = .007), or IDH2 mutations (P = .03) were more likely to respond, and those with TP53 mutations (P = .03) were less likely to respond. The recommended phase 2 dose of AZA is 75 mg/m2 per day on days 1 to 5 followed by HiDAC (3000 mg/m2) and mitoxantrone (30 mg/m2) once each on days 6 and 10. This trial was registered at www.clinicaltrials.gov as #NCT01839240.

Clinical Study Of Dose-Adjusted EPOCH Regimen For Non-Hodgkin's Lymphoma With Hemophagocytic Lymphohistiocytosis: Preliminary Results Of An Ongoing Phase II Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4360-4360
Author(s):  
Wei Xu ◽  
Lei Fan ◽  
Li Wang ◽  
Ji Xu ◽  
Run Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Disease Progression ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Hodgkin’S Lymphoma ◽  
Chemotherapy Regimen ◽  
Hodgkin's Lymphoma ◽  
Phase 2 ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Ongoing Phase

Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS) is characterized by cytokines storm and uncontrolled activation of macrophages. Secondary HLH in adults may occur in different occasions, including infections, autoimmune diseases, carcinomas and hematologic malignancies, in which Lymphoma-associated hemophagocytic lymphohistiocytosis(LA-HLH) has a high fatality rate and the worst outcome. The major cause of LA-HLH is aggressive non-Hodgkin's lymphoma (NHL), especially T/NKT cell lymphomas. Until now, there is no recommended therapeutic schedule for this fatal disease. Because of promising results of etoposide-containing regimen for HLH and high effective of continuous infusion chemotherapy regimen for aggressive NHL .The investigators therefore employed an intensive chemotherapy regimen--DA-EPOCH regimen (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) to treat non-Hodgkin's lymphoma with hemophagocytic lymphohistiocytosis and we have performed a preliminary analysis of this ongoing Phase 2 study and evaluated safety and efficacy of this regimen. Methods The clinical trial was designed as a prospective, multicenter, single-arm phase 2 clinical trial (NCT01818908). Enrolled patients included those with previously untreated NHL, and met the diagnostic criteria of either HLH2004 or ASH 2009 of HLH, patients with primary HLH and secondary HLH other than NHL were excluded. Therapeutic protocol of DA-EPOCH regimen was as follows: etoposide 50 mg/m2 CI 24h d1-d4, doxorubicin 10 mg/m2 CI 24h d1-d4, vincristine 0.4 mg/m2 CI 24h d1-d4, cyclophosphamide 750 mg/m2 IV d5, prednisone 60 mg/m2 oral d1-d5, If enrolled patient was histologically confirmed CD20+ B cell lymphoma, standard dose of rituximab will be recommended to combine with DA-EPOCH regimen. Drug dose was adjusted as previously described (Wyndham H. et al, 2002), each cycle of treatment was administered every 21 to 28 days according to recovery of toxicities. For patients who responded to the treatment and did not have disease progression, interim evaluation was conducted after 3 cycles of treatment. Results At the time of analysis 26 patients were enrolled and 20 patients were eligible to evaluate. Patients were 60.0% (12/20) male with median age 44(range: 14-60), the age-adjusted international prognostic score (aaIPI) enrolled to study was high/intermediate (2 score) 10/20, high risk group (3 score) 10/20. Histologies were four B-NHL, ten T-NHL and six NK-NHL. The median number of cycles of therapy was 3, patients who had discontinued study were mainly due to rapid disease progression. The overall response rate (ORR) among treated pts was 50.0%, with 35.0% (7/20) of patients achieving CR/CRu and 15.0% (3/20) achieving PR, and 50.0% of patients (10/20) had PD. With the median follow-up of 8 months, progression-free survival (PFS) rate was 46.3% and in subgroup analysis, PFS of B-NHL, T-NHL and NK-NHL was 75%, 45.7% and 25% respectively (Fig. 1); Overall survival (OS) rate was 52.4%(Fig. 2) and 75.0%, 58.3%, 22.2% in subgroup of B-NHL, T-NHL and NK-NHL(Fig. 3). The most common grade ≥3 treatment-related side effects were hematologic toxicities including neutropenia and thrombocytopenia. Conclusions Lymphoma-associated hemophagocytic lymphohistiocytosis progresses rapidly and has a high mortality rate, our preliminary results suggest DA-EPOCH regimen has acceptable toxicities and promising activity in NHL with HLH, especially for B-NHL and T-NHL, but prognosis of NK-NHL with HLH remains dismal, urgent need for novel therapeutic strategies may benefit the survival of patients with this disease. Disclosures: No relevant conflicts of interest to declare.

A phase 2 study of prostate specific membrane antigen antibody drug conjugate (PSMA ADC) in patients (pts) with progressive metastatic castration-resistant prostate cancer (mCRPC) following abiraterone and/or enzalutamide (abi/enz).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 144-144 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
Nicholas J. Vogelzang ◽  
Gurkamal S. Chatta ◽  
Mark T. Fleming ◽  
David C. Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Tumor Imaging ◽  
Phase 1 ◽  
Serum Markers ◽  
Electrolyte Imbalance ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Antibody Drug Conjugate ◽  
Phase 2 Trial

144 Background: PSMA is a validated target that is overexpressed selectively on prostate cancer cells. PSMA ADC is a fully human IgG1 antibody conjugated to the microtubule disrupting agent MMAE which binds to PSMA-positive cells, inducing cytotoxicity. A phase 1 study showed activity and tolerability at doses from 1.8-2.5 mg/kg. We have enrolled 119 mCRPC pts who progressed following abi/enz in a phase 2 trial of PSMA ADC. Methods: mCRPC pts (83 taxane experienced (TE) and 36 chemo-naïve (CN)) were administered PSMA ADC 2.5 or 2.3 mg/kg IV Q3 wk for up to 8 cycles. 95% of pts received prior abi and/or enz treatment. Safety, antitumor activity (including PSA, CTCs, and tumor imaging) and exploratory biomarkers were assessed. Results: In all treated pts, PSA declines of ≥30% and ≥50% were 30% and 14%, respectively (n=113); CTC counts showed a decline of ≥50% in 78% of pts and conversion from ≥5 to <5 cells/7.5 ml blood in 47% (n=77) at any time during the study. For 2.3 mg/kg pts (n=82), corresponding PSA declines were 35% and 17%; CTC declines of ≥50% were seen in 81% and conversions in 46% (n=54). For CN pts, PSA declines of ≥30% and ≥50% were 31% and 20% (n=35); CTC declines of ≥50% were seen in 89% and conversion in 53% (n=19). Radiologic response by RECIST in 31 pts with measurable target lesions: PR in 4 pts, SD in 19 pts, and PD in 8 pts. Efficacy responses were associated with: low neuroendocrine serum markers (low CgA, low NSE, and high PSA), high PSMA expression (CTCs or tumor tissue). The most common treatment-related AEs ≥CTCAE grade 3 were neutropenia (TE: 25%; CN: 22%), fatigue (20%; 8%), electrolyte imbalance (16%; 11%), anemia (10%; 8%), and neuropathy (8%; 8%). Grade 1-2 neuropathy occurred in 40% (TE) and 50% (CN) of pts. Two 2.5 mg/kg pts (n=34) and one 2.3 mg/kg pt (n=85) died of sepsis. 2.3 mg/kg was better tolerated than 2.5 mg/kg. Conclusions: PSMA ADC was active in abi/enz refractory mCRPC pts. Clinically significant AEs included neutropenia and neuropathy. CTC conversions/reductions, PSA declines, and radiologic evidence of antitumor activity were seen in CN as well as heavily pretreated pts. Clinical trial information: NCT01695044.

A phase 2 study of BGJ398 in patients (pts) with advanced or metastatic FGFR-altered cholangiocarcinoma (CCA) who failed or are intolerant to platinum-based chemotherapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 335-335 ◽  
Author(s):  
Milind M. Javle ◽  
Rachna T. Shroff ◽  
Andrew Zhu ◽  
Saeed Sadeghi ◽  
SuPin Choo ◽  
...  
Keyword(s):  
Phase 1 ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Phase 2 ◽  
Open Label ◽  
Overall Response ◽  
Platinum Based Chemotherapy ◽  
Metastatic Setting

335 Background: CCA is a hepatobiliary malignancy with poor prognosis and few treatment options following cytotoxic therapy in the first-line metastatic setting. The fibroblast growth factor receptor (FGFR) axis may promote CCA tumorigenesis. FGFR2 fusions (in up to 17% of intrahepatic CCAs) may predict FGFR inhibitor sensitivity. A prior phase 1 trial of the selective pan-FGFR inhibitor BGJ398 showed antitumor activity in a pt with CCA harboring an FGFR2 fusion. Methods: This ongoing phase 2, open-label study is evaluating oral BGJ398 125 mg once daily on a 3-week-on/1-week-off schedule (28-day cycle) in pts with advanced or metastatic CCA with FGFR2 fusions (n ≈ 40) or other FGFR genetic alterations (n ≤ 15) who progressed after cisplatin/gemcitabine or are cisplatin intolerant (NCT02150967). The primary endpoint is investigator-assessed overall response rate (ORR) per RECIST v1.1. Secondary endpoints include progression-free survival, best overall response (BOR), disease control rate (DCR), overall survival, safety, and pharmacokinetics. Results: As of 10 July 2015, 26 pts with CCA harboring FGFR2 fusions (n = 22) or other FGFR alterations (n = 4), pretreated with 1 to ≥ 4 prior regimens, were enrolled. Common adverse events (AEs; ≥ 20% of pts), were hyperphosphatemia (50%), fatigue (42%), constipation (38%), cough (23%), and nausea (23%). Grade 3/4 AEs occurring in ≥ 2 pts were hyper/hypophosphatemia, lipase increase, and hyponatremia. AEs were manageable, reversible, and rarely led to treatment discontinuation. Among 22 pts evaluable for BOR, 3 achieved partial response and 15 had stable disease, including 10 with tumor reductions (-41%, n = 1; -2% to -29%, n = 9). Overall DCR was 82%. As of the cutoff date, 18 pts remained on therapy, of which 13 were on for > 120 days. Kaplan-Meier estimated lower limit (95% CI) of median time on study was 143 days. Conclusions: BGJ398 shows impressive anti-tumor activity and a manageable safety profile in pts with advanced FGFR-altered CCA, an indication of high unmet medical need. Updated data including additional responses post data cutoff will be presented. Clinical trial information: NCT02150967.

Updated results of a phase 1 study combining the matrix metalloproteinase 9 inhibitor GS-5745 with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 363-363 ◽  
Author(s):  
Johanna C. Bendell ◽  
Manish R. Patel ◽  
Carrie Baker Brachmann ◽  
Xi Huang ◽  
Julia D. Maltzman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Matrix Metalloproteinase ◽  
Pancreatic Adenocarcinoma ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Matrix Metalloproteinase 9 ◽  
Phase 1 Study ◽  
Metastatic Setting ◽  
Metalloproteinase 9

363 Background: GS-5745 is a monoclonal antibody inhibitor of matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. We present data from patients (pts) with advanced pancreatic adenocarcinoma enrolled in an ongoing multi-indication phase 1 study (NCT01803282) evaluating GS-5745. Methods: Following a monotherapy dose finding stage, pts with locally advanced or metastatic pancreatic cancer received gemcitabine (G) + nab-paclitaxel (Abraxane, A) and GS-5745 800 mg IV every 2 weeks. Treatment continued until disease progression, unacceptable toxicity or withdrawal of consent. Response was assessed every 8 weeks per RECIST version 1.1 criteria. Results: As of April 2016, 36 pts were enrolled (1 continues to receive GS-5745). The most frequently observed adverse events (AEs) of any grade include fatigue (75%), alopecia (55.6%), peripheral edema (55.6%) and nausea (50%). Grade ≥ 3 AEs observed in ≥ 10% of pts included neutropenia (25%), anemia (19.4%) and fatigue (13.9%). The median progression free survival (PFS) for all pts is 7.8 (90% confidence interval (CI) = [6.1, 11]) months (mos), median duration of response (DOR) is 5.8 mos and the objective response rate (ORR) is 44.4%. Of the 31 pts who were treatment naïve in the metastatic setting, median PFS is 9.2 (90% CI = [6.1, 11]) mos, median DOR 5.8 mos and the ORR 51.6%. Median baseline circulating MMP9 was 44.3 (range 12.4-549.6) ng/mL and 31 of 32 patients with post-baseline samples had undetectable MMP9 levels within 8 weeks. Conclusions: GS-5745+GA demonstrated numerically higher ORR and PFS compared to historical data without additional toxicity. Additionally, reductions in circulating MMP9 levels post treatment suggest target engagement by GS-5745 . These results suggest this combination may warrant additional study in first line metastatic pancreatic adenocarcinoma. Clinical trial information: NCT01803282.

Primary analysis of phase 2 results of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with locally advanced cutaneous squamous cell carcinoma (laCSCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6015-6015 ◽  
Author(s):  
Michael Robert Migden ◽  
Nikhil I. Khushalani ◽  
Anne Lynn S. Chang ◽  
Danny Rischin ◽  
Chrysalyne D. Schmults ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Median Duration ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase 2 ◽  
Primary Analysis ◽  
Curative Surgery ◽  
Grade 3

6015 Background: Cemiplimab (REGN2810) produced substantial antitumor activity with durable responses in Phase 1 CSCC expansion cohorts and Phase 2 metastatic (m) CSCC cohort. We now present the primary analysis of the Phase 2 laCSCC cohort (NCT02760498; data cutoff date: Oct 10, 2018). Methods: Pts with laCSCC received cemiplimab 3 mg/kg IV every 2 weeks (Q2W). Tumor measurements were performed Q8W. The primary objective was to evaluate objective response rate (ORR; complete response [CR] + partial response [PR]) according to independent central review (per RECIST 1.1 for scans; modified WHO criteria for photos). Results: 78 pts were enrolled (59 M/ 19 F; median age: 74 years; ECOG PS: 0 in 38 pts, 1 in 40 pts; primary CSCC site: head/neck in 79.5%; prior systemic therapy: 15.4%; prior radiotherapy: 55.1%). Median duration of follow-up was 9.3 months (range: 0.8–27.9). ORR by central review was 43.6% (95% CI: 32.4–55.3; 10 CRs and 24 PRs); investigator-assessed (INV) ORR was 52.6% (95% CI: 40.9–64.0; 13 CRs and 28 PRs). Median duration of response (DOR) has not been reached. The longest DOR at data cut-off was 24.2 months and was still ongoing. Durable disease control rate (stable disease or response for ≥16 weeks) was 62.8% (95% CI: 51.1–73.5). Median observed time to response was 1.9 months (range: 1.8–8.8). Median progression-free and overall survival have not been reached. Tumor PD-L1 status is available for 48/78 pts, tumor mutational burden analysis (from targeted exome panel) is ongoing for ≥40/78 pts; response correlation analyses are planned. The most common treatment-emergent adverse events (AEs; all grades, Grade ≥3) were fatigue (42.3%, 1.3%), diarrhea and pruritus (both 26.9%, 0%), and nausea (21.8%, 0%). INV grade ≥3 immune-related AEs occurred in 10.3% of pts. One pt died due to an unknown cause that was assessed as treatment-related. Conclusions: Cemiplimab 3 mg/kg Q2W showed substantial antitumor activity, durable responses, and acceptable safety profile in pts with laCSCC. These data strongly support the recent FDA approval of cemiplimab-rwlc for pts with mCSCC or laCSCC who are not candidates for curative surgery or curative radiation. Clinical trial information: NCT02760498.

FOENIX-CCA2: A phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 108-108 ◽  
Author(s):  
Lipika Goyal ◽  
Funda Meric-Bernstam ◽  
Antoine Hollebecque ◽  
Juan W. Valle ◽  
Chigusa Morizane ◽  
...  
Keyword(s):  
Disease Progression ◽  
Intrahepatic Cholangiocarcinoma ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Gene Fusions ◽  
Phase 2 ◽  
Fgfr2 Gene ◽  
Platinum Based Chemotherapy ◽  
Grade 3

108 Background: Patients (pts) with intrahepatic cholangiocarcinoma (iCCA) have a 5-year survival rate of 24%. There is no standard treatment for advanced disease after first-line chemotherapy. Fibroblast growth factor receptor-2 ( FGFR2) gene fusions occur in 10% to 20% of pts with iCCA, offering a promising therapeutic avenue for this disease. Futibatinib is a highly selective irreversible FGFR1-4 inhibitor given as a continuous once-daily (QD) oral regimen. This phase 2 registrational trial was initiated because of results from a phase 1 dose escalation/expansion study showing tolerability and preliminary efficacy of futibatinib in pts with iCCA with FGFR2 fusions. Methods: FOENIX-CCA2 (NCT02052778), a single-arm multicenter phase 2 study, enrolled pts with locally advanced/metastatic unresectable iCCA harboring FGFR2 gene fusions or other rearrangements, disease progression after ≥1 line of systemic therapy (including gemcitabine plus platinum-based chemotherapy), no prior FGFR inhibitor treatment, and an ECOG performance status of 0 or 1. Pts received futibatinib 20 mg QD until disease progression/unacceptable toxicity. The primary endpoint is objective response rate (ORR) based on independent central radiology review. Secondary endpoints include disease control rate (DCR), duration of response (DOR), and safety. Results: A total of 103 pts were enrolled. For this interim analysis, data are reported for the 67 pts (65%) with ≥6 months of follow-up. Of these, 82.1% of pts had tumors harboring an FGFR2 fusion. One, 2, or ≥3 prior therapies were received by 44.8%, 28.4%, and 26.9% of pts, respectively. ORR was 34.3% (all partial response, n = 23), and DCR was 76.1%; assessment was pending for 8 pts. Median time to response was 1.6 months (range, 1.0-4.9), and median DOR was 6.2 months (range, 2.1-14.2). The most common treatment-related adverse events (AEs; all grade, grade ≥3) were hyperphosphatemia (79.1%, 25.4%), diarrhea (37.3%, 0%), and dry mouth (32.8%, 0%). Any-cause grade ≥3 AEs were reported in 73.1% of pts. Dose delay or dose reduction was required in 65.7% and 53.7% of pts, respectively; 6.0% of pts discontinued treatment because of AEs. Conclusions: Preliminary assessment of these phase 2 data indicate efficacy and tolerability of futibatinib for treatment of pts with iCCA harboring FGFR2 fusions or other rearrangements who have progressed after chemotherapy. Continued analysis of the study population is underway. Clinical trial information: NCT02052778.

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