Tepotinib in patients (pts) with advanced non-small cell lung cancer (NSCLC) with MET amplification (METamp).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9021-9021
Author(s):  
Xiuning Le ◽  
Luis G. Paz-Ares ◽  
Jan Van Meerbeeck ◽  
Santiago Viteri ◽  
Carlos Cabrera Galvez ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Group Performance ◽  
Objective Response ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Gene Copy ◽  
Durable Response ◽  
Met Inhibitor ◽  
Grade 3 ◽  
Ecog Ps

9021 Background: METamp is an oncogenic driver occurring in 1–5% of NSCLCs that confers a poor prognosis and lacks approved targeted therapies. Tepotinib, a highly selective MET inhibitor, provided durable response in NSCLC with MET exon 14 ( METex14) skipping in Cohort A of the Phase II VISION trial (NCT02864992). VISION Cohort B evaluated tepotinib in pts with advanced NSCLC and METamp, as detected by a convenient and minimally invasive liquid biopsy assay, in the absence of METex14 skipping. Methods: Pts with locally advanced or metastatic NSCLC, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, 0–2 prior lines of therapy, EGFR/ ALK wild-type status, no METex14 skipping, and METamp by liquid biopsy (Guardant360®; MET gene copy number ≥2.5) received oral tepotinib 500 mg QD (450 mg active moiety). The primary endpoint was objective response (RECIST v1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DOR), progression-free survival (PFS) and safety. The data cut-off was July 1, 2020. Results: Among 24 enrolled pts, median age was 63.4 years (range: 38–73), 21 pts (88%) were male, 21 (88%) had ECOG PS 1 and 21 (88%) were smokers. Tepotinib was given to 7 pts (29%) in first line (1L), 10 pts (42%) in second line (2L) and 7 pts (29%) in third line (3L). As of November 2020, treatment was ongoing for > 1 year in 5 pts (1L, n = 2; 2L, n = 2; 3L, n = 1). Objective response rate (ORR) by IRC was 42% (10/24 pts) overall, 71% (5/7 pts) in 1L, 30% (3/10 pts) in 2L and 29% (2/7 pts) in 3L (Table). Median DOR by IRC was not estimable (NE; 95% confidence interval [CI]: 2.8 months–NE). Investigator-assessed outcomes were similar. Five pts (20.8%) discontinued due to adverse events (AEs), which were considered unrelated to tepotinib. Treatment-related AEs were reported in 16 pts (67%; Grade 3/4, 7 pts [29%]) and included peripheral edema (9 pts [38%]; Grade 3/4, 2 pts [8%]), generalized edema (4 pts [17%]; Grade 3/4, 2 pts [8%]) and constipation (4 pts [17%]; Grade 3/4, 0 pts). Conclusions: In the first study of a MET inhibitor in NSCLC with METamp prospectively detected by liquid biopsy, tepotinib showed high and clinically meaningful activity, especially in 1L, and was generally well tolerated. Tepotinib warrants further evaluation in NSCLC with METamp. Clinical trial information: NCT02864992. [Table: see text]

scholarly journals Avelumab in Combination with Axitinib as First-Line Treatment in Patients with Advanced Hepatocellular Carcinoma: Results from the Phase 1b VEGF Liver 100 Trial

Liver Cancer ◽  
2021 ◽  
pp. 1-11
Author(s):  
Masatoshi Kudo ◽  
Kenta Motomura ◽  
Yoshiyuki Wada ◽  
Yoshitaka Inaba ◽  
Yasunari Sakamoto ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Group Performance ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Clinical Activity ◽  
Advanced Hepatocellular Carcinoma ◽  
Recist 1.1 ◽  
Phase 1B ◽  
Grade 3

<b><i>Introduction:</i></b> Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC. <b><i>Methods:</i></b> Eligible patients had confirmed aHCC, no prior systemic therapy, ≥1 measurable lesion, Eastern Cooperative Oncology Group performance status ≤1, and Child-Pugh class A disease. Patients received avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and investigator-assessed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) for HCC. <b><i>Results:</i></b> Twenty-two Japanese patients were enrolled and treated with avelumab plus axitinib. The minimum follow-up was 18 months as of October 25, 2019 (data cutoff). Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (72.7%); the most common (≥3 patients) were hypertension (<i>n</i> = 11 [50.0%]), palmar-plantar erythrodysesthesia syndrome (<i>n</i> = 5 [22.7%]), and decreased appetite (<i>n</i> = 3 [13.6%]). No grade 4 TRAEs or treatment-related deaths occurred. Ten patients (45.5%) had an immune-related AE (irAE) of any grade; 3 patients (13.6%) had an infusion-related reaction (IRR) of any grade, and no grade ≥3 irAE and IRR were observed. The objective response rate was 13.6% (95% CI: 2.9–34.9%) per RECIST 1.1 and 31.8% (95% CI: 13.9–54.9%) per mRECIST for HCC. <b><i>Conclusion:</i></b> Treatment with avelumab plus axitinib was associated with a manageable toxicity profile and showed antitumor activity in patients with aHCC.

TROPiCS-04: Study of sacituzumab govitecan in metastatic or locally advanced unresectable urothelial cancer that has progressed after platinum and checkpoint inhibitor therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS498-TPS498
Author(s):  
Petros Grivas ◽  
Scott T. Tagawa ◽  
Joaquim Bellmunt ◽  
Maria De Santis ◽  
Ignacio Duran ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Topoisomerase I ◽  
Progressive Disease ◽  
Group Performance ◽  
Checkpoint Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii

TPS498 Background: Treatment options are limited for patients with locally advanced unresectable or metastatic urothelial carcinoma (mUC) who progress following prior platinum-based and checkpoint inhibitor (CPI) therapy. Sacituzumab govitecan (SG) is an antibody-drug conjugate consisting of an anti–Trop-2 monoclonal antibody coupled to SN-38 (an active metabolite of irinotecan, a topoisomerase-I inhibitor) via a unique hydrolyzable linker. A phase II registrational study, TROPHY-U-01 study, confirmed the initial positive efficacy signal in mUC. SG demonstrated an objective response rate (ORR) of 27% and median overall survival (OS) of 10.5 months in patients with mUC (median 3 prior lines of therapy and 87% with ≥1 Bellmunt risk factors) who progressed after prior platinum-based and CPI therapies (n=113; Loriot ESMO 2020). The results compared favorably with historic single-agent chemotherapy (ORR ~10%; OS ≤7 months). A phase III trial has been initiated to confirm these findings. Methods: TROPiCS-04 (NCT04527991) is a global, multicenter, open-label, randomized, controlled trial in patients with locally advanced unresectable or mUC who progressed after prior platinum-based and CPI therapies (with Eastern Cooperative Oncology Group performance status 0–1 and adequate hematologic, hepatic, and renal function). Patients will be randomized 1:1 to receive SG 10 mg/kg intravenously (IV) on day 1 and 8 of 21-day cycles or single-agent treatment of physician’s choice (paclitaxel 175 mg/m2, docetaxel 75 mg/m2, or vinflunine 320 mg/m2 IV on day 1 of 21-day cycles) until progressive disease, unacceptable toxicity, or withdrawal of consent. Treatment beyond progressive disease may be permitted in patients deemed to be receiving clinical benefit per investigator assessment. Approximately 482 patients will be enrolled to provide 90% power on the primary endpoint of OS. Secondary endpoints include progression-free survival, ORR, clinical benefit rate, duration of response (all per Response Evaluation Criteria in Solid Tumors v1.1), safety, and quality of life. Study initiation is ongoing and enrollment begins in Q4 2020 across ~90 sites. Clinical trial information: NCT04527991.

EAGLE: A phase 3, randomized, open-label study of durvalumab (D) with or without tremelimumab (T) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6012-6012 ◽  
Author(s):  
Lisa F. Licitra ◽  
Robert I. Haddad ◽  
Caroline Even ◽  
Makoto Tahara ◽  
Mikhail Dvorkin ◽  
...  
Keyword(s):  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Standard Of Care ◽  
Open Label ◽  
Phase 3 ◽  
Risk Of Death ◽  
Grade 3

6012 Background: EAGLE is a phase 3 study evaluating efficacy of D (anti-PD-L1 mAb) monotherapy and D+T (anti-CTLA-4 mAb) vs standard of care (SOC) in pts with R/M HNSCC who progressed following platinum-based therapy (NCT02369874). Methods: Pts were randomized 1:1:1 to D 10 mg/kg IV every 2 weeks (Q2W), D+T (D 20 mg/kg IV Q4W + T 1 mg/kg IV Q4W for 4 doses, then D 10 mg/kg IV Q2W), or SOC (investigator’s choice: cetuximab, taxane, methotrexate, or fluoropyrimidine-based regimen). The primary endpoint was overall survival (OS) with dual primary objectives of D+T vs SOC and D vs SOC. Additional endpoints included objective response rate (ORR), duration of response (DoR), and adverse events (AEs). Results: 240 pts were randomized to D, 247 to D+T and 249 to SOC. An imbalance for Eastern Cooperative Oncology Group performance status (ECOG PS) was seen in favor of the SOC arm (D, PS 0 = 26%, PS 1 = 74%; D+T, PS 0 = 26%, PS 1 = 74%; SOC, PS 0 = 32%, PS 1 = 68%). The risk of death was not statistically significantly different for D compared with SOC (HR: 0.88; 95% CI: 0.72–1.08; P = 0.20) or D+T vs SOC (HR: 1.04; 95% CI: 0.85–1.26; P = 0.76). Efficacy data are provided in the table. Treatment-related AEs Grade ≥3 were reported in 10.1% of pts (regardless of causality Grade ≥3 AEs were 41.4%) in the D arm, 16.3% (51.2%) for D+T, and 24.2% (44.2%) for SOC. Following treatment, 2% of pts in D, 5% in D+T and 15% in SOC received immunotherapy. Conclusions: D and D+T did not demonstrate a statistically significant improvement in OS compared to standard chemotherapy in pts with R/M HNSCC. Median OS and ORR of D arm were similar to other studies with checkpoint inhibitors. The SOC arm outperformed what has been seen for SOC arms in previous studies; subsequent immunotherapy may have confounded the OS analyses. The safety profile for D and D + T in R/M HNSCC is consistent with previous trials. Clinical trial information: NCT02369874. [Table: see text]

Influence of tumor size and Eastern Cooperative Oncology Group performance status (ECOG PS) at baseline on patient (pt) outcomes in lenvatinib-treated radioiodine-refractory differentiated thyroid cancer (RR-DTC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6081-6081 ◽  
Author(s):  
Lori J. Wirth ◽  
Sophie Leboulleux ◽  
Naomi Kiyota ◽  
Makoto Tahara ◽  
Kei Muro ◽  
...  
Keyword(s):  
Tumor Size ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Disease Characteristics ◽  
Kaplan Meier ◽  
Ecog Ps ◽  
Post Hoc

6081 Background: In SELECT, lenvatinib significantly improved progression-free survival (PFS) of pts with RR-DTC versus placebo (18.3 v 3.6 months; hazard ratio [HR]: 0.21 [99% CI: 0.14, 0.31]; P<0.001). Here we examine the treatment of RR-DTC with lenvatinib in relation to tumor size (sum of all targeted lesions) and ECOG PS. Methods: In this post hoc analysis of SELECT with pts randomized to receive lenvatinib, Kaplan-Meier estimates of time to ECOG PS ≥2 were calculated for subgroups of pts according to baseline ECOG PS or tumor size. Objective response rate (ORR) and Kaplan-Meier estimates of overall survival (OS) and PFS according to ECOG PS (0 or 1) at baseline were calculated. Correlations between ECOG PS at baseline (0 or 1) and maximum tumor shrinkage were calculated using one-way analysis of variance. Results: Pts with ECOG PS 0 or 1 at baseline had similar demographic and disease characteristics. ORR was 78.5% and 51.0% for pts with ECOG PS 0 and 1 at baseline, respectively (odds ratio [95% CI]: 3.508 [2.018, 6.097]). Mean maximum percent decrease in tumor size was significantly greater in pts with baseline ECOG PS 0 (-46.13%) versus pts with ECOG PS 1 (-37.16%; P=0.0017). For pts with ECOG PS 1 at baseline, time to ECOG PS ≥2 was numerically shorter with tumor size >60 mm versus tumor size ≤60 mm (HR [95% CI]: 1.450 [0.708, 2.967]). Additional results are summarized in the table. Conclusions: Among pts with RR-DTC, PFS, OS, ORR, and time to ECOG ≥2 were generally better for patients with lower ECOG PS or smaller tumor size at baseline. These results may indicate that it is beneficial to start lenvatinib in pts with RR-DTC early, before ECOG PS worsens and tumor size increases. Clinical trial information: NCT01321554. [Table: see text]

XENERA-1: A phase II trial of xentuzumab (Xe) in combination with everolimus (Ev) and exemestane (Ex) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) and non-visceral involvement.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS1103-TPS1103 ◽  
Author(s):  
Peter Schmid ◽  
Hope S. Rugo ◽  
Javier Cortes ◽  
Chin-Lun Huang ◽  
Kate Crossley ◽  
...  
Keyword(s):  
Growth Factor ◽  
Disease Control ◽  
Phase Ii ◽  
Group Performance ◽  
Objective Response ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Menopausal Women ◽  
Post Menopausal ◽  
Visceral Disease

TPS1103 Background: The mTOR inhibitor Ev, combined with Ex, is a mainstay in the treatment of post-menopausal women with advanced HR+/HER2- BC. However, the activity of Ev is limited by counter-regulatory feedback mechanisms in cancer cells, involving reactivation of insulin-like growth factor (IGF)/mTOR survival signaling. Combining Ev with the humanized IGF-1 and IGF-2 ligand-blocking antibody Xe abrogates this feedback, thus intensifying inhibition of tumor growth; this leads to a pronounced effect in patients with non-visceral (e.g., bone and lymph node) metastases. The phase II XENERA-1 trial evaluates the combination of Xe with Ev and Ex in post-menopausal women with HR+/HER2- BC. Methods: XENERA-1 (NCT03659136) is a double-blind, placebo-controlled, randomized study to assess the efficacy and safety of Xe in combination with Ev and Ex, in post-menopausal women with HR+/HER2- locally advanced/mBC and non-visceral disease. The population comprises post-menopausal mBC patients who have progressed on ≤1 previous line of a non-steroidal aromatase inhibitor, with or without a CDK 4/6 inhibitor, who may have received fulvestrant. Other inclusion criteria are: an Eastern Cooperative Oncology Group Performance Status of 0 or 1; adequate organ function; and non-visceral disease (absence of brain, liver, lung, peritoneal or pleural metastases). Patients are randomized (1:1) to receive Xe (1000 mg/week, iv) or placebo (weekly, iv), in combination with Ev (10 mg/day) and Ex (25 mg/day). Treatment will continue until disease progression, unacceptable toxicity or other reasons. The primary endpoint is progression-free survival according to RECIST 1.1 criteria, by independent review. Secondary endpoints are: overall survival; disease control; duration of disease control; objective response; and time to progression of pain/intensification of palliation. Safety and pharmacokinetic endpoints, and exploratory biomarkers will also be evaluated. The first patient was enrolled in January 2019; target enrollment is 80 patients in 12 countries. Clinical trial information: NCT03659136.

scholarly journals Digital Detection of Sarcopenia in Pancreatic Cancer: Additional Utilization to Plan Patient Management

2021 ◽  
Author(s):  
Mustafa Jalal ◽  
Jennifer A Campbell ◽  
Jonathan Wadsley ◽  
Andrew D Hopper
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Skeletal Muscle Index ◽  
Ecog Ps ◽  
Cancer Network

Abstract Purpose: The presence of a sarcopenia adversely affects the prognosis of patients with pancreatic cancer. There is an emerging role for using computed tomography (CT) to calculate skeletal muscle index (SMI) and the presence of sarcopenia. The aim of this study was to assess if detecting ‘digital sarcopenia’ is feasible and can contribute to the management of patients with locally advanced pancreatic cancer (LAPC).Methods: Patients diagnosed with LAPC referred for endoscopic ultrasound guided biopsy (EUS-B) by our regional cancer network were identified. Age, body mass index (BMI), and Eastern Cooperative Oncology Group performance status (ECOG-PS) was noted. CT images were analysed for SMI and the presence of sarcopenia. Decision outcomes on receiving chemotherapy or not were collected from the regional oncology database. Results: In total 51/204 (25%) patients with LAPC who underwent EUS-B were not given chemotherapy and received BSC only. The prevalence of sarcopenia (p=0.0003), age ≥ 75 years old (p=0.03) and ECOG-PS 2-3 (p=0.01) were significantly higher in the patents receiving BSC only. Logistic regression analysis demonstrated that SMI was the only independent associated factor identifying patients with LAPC who were treated with BSC only and not chemotherapy after adjusting for age and ECOG-PS. Conclusion: Our study has shown that digital skeletal muscle analysis at the time of a diagnostic CT for patients with pancreatic cancer is feasible and can detect sarcopenia and malnourished patients who are much less likely to take up chemotherapy. These patients could be triaged to oncology assessment prior to EUS-B to avoid unnecessary investigations.

scholarly journals Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Jose Pablo Leone ◽  
Kyrre E. Emblem ◽  
Michelle Weitz ◽  
Rebecca S. Gelman ◽  
Bryan P. Schneider ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Group Performance ◽  
Brain Mri ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Her2 Positive ◽  
Breast Cancer Brain Metastases ◽  
Ecog Ps ◽  
Mri Changes

Abstract Background We aimed to examine the safety and efficacy of bevacizumab and carboplatin in patients with breast cancer brain metastases. Methods We enrolled patients with breast cancer and > 1 measurable new or progressive brain metastasis. Patients received bevacizumab 15 mg/kg intravenously (IV) on cycle 1 day 1 and carboplatin IV AUC = 5 on cycle 1 day 8. Patients with HER2-positive disease also received trastuzumab. In subsequent cycles, all drugs were administered on day 1 of each cycle. Contrast-enhanced brain MRI was performed at baseline, 24–96 h after the first bevacizumab dose (day + 1), and every 2 cycles. The primary endpoint was objective response rate in the central nervous system (CNS ORR) by composite criteria. Associations between germline VEGF single nucleotide polymorphisms (rs699947, rs2019063, rs1570360, rs833061) and progression-free survival (PFS) and overall survival (OS) were explored, as were associations between early (day + 1) MRI changes and outcomes. Results Thirty-eight patients were enrolled (29 HER2-positive, 9 HER2-negative); all were evaluable for response. The CNS ORR was 63% (95% CI, 46–78). Median PFS was 5.62 months and median OS was 14.10 months. As compared with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, patients with ECOG PS 1–2 had significantly worse PFS and OS (all P < 0.01). No significant associations between VEGF genotypes or early MRI changes and clinical outcomes were observed. Conclusions The combination of bevacizumab and carboplatin results in a high rate of durable objective response in patients with brain metastases from breast cancer. This regimen warrants further investigation. Trial registration NCT01004172. Registered 28 October 2009.

scholarly journals Computed Tomographic Sarcopenia in Pancreatic Cancer: Further Utilization to Plan Patient Management

2021 ◽  
Author(s):  
Mustafa Jalal ◽  
Jennifer A. Campbell ◽  
Jonathan Wadsley ◽  
Andrew D. Hopper
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Skeletal Muscle Index ◽  
Computed Tomographic ◽  
Ecog Ps

Abstract Purpose The presence of a sarcopenia adversely affects the prognosis of patients with pancreatic cancer. There is an emerging role for using computed tomography (CT) to calculate skeletal muscle index (SMI) and the presence of sarcopenia. The aim of this study was to assess if detecting ‘computed tomographic sarcopenia’ is feasible and can contribute to the management of patients with locally advanced pancreatic cancer (LAPC). Methods Patients diagnosed with LAPC referred for endoscopic ultrasound-guided biopsy (EUS-B) by our regional cancer network were identified. Age, body mass index (BMI), and Eastern Cooperative Oncology Group performance status (ECOG-PS) were noted. CT images were analysed for SMI and the presence of sarcopenia. Decision outcomes on receiving chemotherapy or not were collected from the regional oncology database. Results In total, 51/204 (25%) patients with LAPC who underwent EUS-B were not given chemotherapy and received best supportive care (BSC) only. The prevalence of sarcopenia (p = 0.0003), age ≥ 75 years old (p = 0.03), and ECOG-PS 2–3 (p = 0.01) were significantly higher in the patients receiving BSC only. Logistic regression analysis demonstrated that SMI was the only independent associated factor identifying patients with LAPC who were treated with BSC only and not chemotherapy after adjusting for age and ECOG-PS. Conclusion Our study has shown that computed tomographic skeletal muscle analysis at the time of a diagnostic CT for patients with pancreatic cancer is feasible and can detect sarcopenia and malnourished patients who are much less likely to take up chemotherapy. These patients could be triaged to oncology assessment prior to EUS-B to avoid unnecessary investigations.

Phase II trial of SAR439859 vs endocrine monotherapy in pre- and post-menopausal, estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), locally advanced or metastatic breast cancer (BC) with prior exposure to hormonal therapies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS1107-TPS1107
Author(s):  
Sara M. Tolaney ◽  
Irfan Cicin ◽  
Rafael Betancourt ◽  
Arlene Chan ◽  
Diego Kaen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Response Rate ◽  
Group Performance ◽  
Locally Advanced ◽  
Plasma Concentrations ◽  
Eastern Cooperative Oncology Group ◽  
Metastatic Breast ◽  
Metastatic Setting ◽  
Ecog Ps

TPS1107 Background: Endocrine therapy (ET) targeting ER signaling is the mainstay of care for ER+ metastatic BC. There remains an unmet need in patients (pts) whose tumors become resistant to currently available ET. Selective ER degraders (SERDs) were developed to overcome resistance to existing ER-directed therapies by both competitively antagonizing and degrading ERs, while exploiting continued dependence of the tumor on ER signaling. SAR439859 is a potent SERD with robust preclinical ER degrading activity. In a Phase I dose escalation trial, SAR439859 demonstrated a favorable safety profile with no dose-limiting toxicities across all doses (20–600 mg QD). ER occupancy generally exceeded > 87% with plasma concentrations > 100 ng/mL. Overall response rate was 6.3% and clinical benefit rate was 50% (Campone. SABCS 2019. P5-11-02). The recommended Phase II monotherapy dose was 400 mg QD. Methods: This international, prospective, open-label, randomized Phase II study (NCT04059484; ACT16105) assesses safety and efficacy of SAR439859 in pts with ER+ (> 1%)/HER2- metastatic or locally advanced BC progressing on ≥ 6 months of continuous ET (0–2 lines in the metastatic setting). Prior CDK inhibitors are allowed. Exclusion criteria include Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, life expectancy < 3 months, > 1 chemotherapy or targeted therapy in the metastatic setting, concomitant illness and factors potentially affecting SAR439859 absorption. Pts are randomized 1:1 to SAR439859 400 mg QD orally or physician’s choice of endocrine monotherapy (fulvestrant, tamoxifen, aromatase inhibitor). Pts receive 28-day cycles until unacceptable toxicity, progression, death, investigator decision or pt request. Stratification factors include visceral metastases, prior CDK4/6 inhibitors, and ECOG PS. Primary endpoint is progression-free survival (RECIST v1.1). Secondary endpoints include overall survival, response rate, duration of response, clinical benefit, pharmacokinetics, quality of life and safety. Target enrollment: n = 282; current enrollment: n = 9. Funding: Sanofi Clinical trial information: NCT04059484 .

Neoadjuvant itraconazole (I) in patients (pts) with resectable basal cell carcinoma (BCC): A phase II multistage study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22081-e22081
Author(s):  
Rodrigo Perez Pereira ◽  
Sergio Jobim Azevedo ◽  
Juliano Cé Coelho ◽  
Taiane Francieli Rebelatto ◽  
Gabriela Lusa Viapiana ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
R0 Resection ◽  
Ki 67 ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1

e22081 Background: Targeting the hedgehog (HH) protein family pathway has consistently shown activity in locally advanced and metastatic BCC. Itraconazole is an affordable agent with known toxicity profile that demonstrates in vitro HH signaling inhibition, suggesting a possible role in BCC treatment. Initial results of a phase 2 study designed to investigate efficacy of Itraconazole as neoadjuvant treatment in patients with resectable BCC are reported. Methods: Eligible pts had biopsy-proven resectable BCC, ECOG PS 0-3, adequate organ function and measurable disease. Dosing of I consisted of 200mg twice daily for 60 days followed by surgery. Simon two-stage design was used to test a null rate of 5% vs. 20% (power = 0.80; α = 0.05, unilateral). If ≥1 of 13 pts in stage 1 have objective response (OR) according to RECIST 1.1 criteria, 14 more pts will be enrolled. If ≥4 of 27 pts have OR, the treatment is worthy of further study. Secondary endpoints include safety and change in Ki-67 and Gli1. Results: Thirteen pts with 14 measurable lesions enrolled from Jan/2018 to Feb/2019; 1 pt was not evaluable, but was included in safety analysis. Demographics and outcomes are summarized in Table. After 60 days of treatment, all patients had R0 resection as primary planned and 1 (8.3%) PR was observed. There were no progressions during the study. OR rate was 8.3%. No grade 3 AE or SAE were reported. 6 pts had grade 1 or 2 AEs at least possibly related to I including depression, headache, GPT elevation, diarrhea, abdominal pain and bilirubin elevation. Conclusions: Itraconazole showed initial anti-tumor activity in pts with resectable BCC, no safety concerns were observed. Study will proceed to Simon’s second stage. Clinical Trial Information: NCT03972748 , 47011715.0.0000.5327 . [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document