A phase Ib study of TQB2450 plus anlotinib in patients with advanced triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1074-1074
Author(s):  
Jiayu Wang ◽  
Binghe Xu ◽  
Tao Sun ◽  
Quchang Ouyang ◽  
Yiqun Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Dose Escalation ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Expansion Phase ◽  
Qt Interval Prolongation ◽  
Grade 3

1074 Background: TQB2450 is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). Anlotinib is an antiangiogenic small molecule, multi-target tyrosine kinase inhibitor that has improved clinical outcomes in various solid tumors. This phase 1b study aims to evaluate the safety and efficacy of TQB2450 plus anlotinib for patients with advanced triple-negative breast cancer (TNBC) after the failure of standard therapy. Methods: This ongoing study included a dose-escalation phase and an expansion phase. Advanced TNBC patients with prior anthracyclines and/or taxanes treatment and failed at least first-line therapy were enrolled. In the dose-escalation phase, eligible patients received anlotinib (8mg, 10mg, and 12mg, qd, days 1-14; 21 days per cycle) plus TQB2450 (1200mg, day 1; 21 days per cycle) following the conventional 3+3 design. If the starting dose of 10mg anlotinib led to ≥2 dose-limiting toxicities (DLTs), 8mg anlotinib would be administered. After the dose-escalating phase, eligible patients were enrolled into the expansion cohort. The primary endpoint was objective response rate (ORR), and the secondary endpoints were overall survival (OS), disease control rate (DCR), progression-free survival (PFS), and safety. Results: Between May 29, 2019, and December 31, 2020, in the dose-escalation phase, three patients receiving 10mg anlotinib plus 1200mg TQB2450 had no DLTs in the first cycle, neither did three patients with 12mg anlotinib plus TQB2450. Next, 28 patients with advanced TNBC received 12 mg anlotinib plus TQB2450 in the expansion phase. Finally, a total of 34 patients were included with median age of 49.5 (32-70) and median prior lines of 2 (1-6). Numbers of patients with prior platinum therapy: 16, prior anthracycline therapy: 32. The ORR was 26.47% (9/34) and DCR was 82.35% (28/34). The median PFS was 8.57 months. Seventeen patients experienced grade 3 treatment-related AEs (TRAEs). Most frequently occurring (>5%) grade 3 TRAEs were QT interval prolongation (17.65%), hypertension (14.71%), diarrhea (8.82%), hand-foot syndrome (HFS) (8.82%), and hypertriglyceridemia (5.88%). Conclusions: TQB2450 plus anlotinib showed an acceptable safety profile with promising activity for previously anthracyclines and/or taxanes-treated advanced TNBC patients. Clinical trial information: NCT03855358 .[Table: see text]

scholarly journals Glembatumumab vedotin for patients with metastatic, gpNMB overexpressing, triple-negative breast cancer (“METRIC”): a randomized multicenter study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Linda T. Vahdat ◽  
Peter Schmid ◽  
Andres Forero-Torres ◽  
Kimberly Blackwell ◽  
Melinda L. Telli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Primary Endpoint ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Common Grade ◽  
Open Label Phase ◽  
Grade 3

AbstractThe METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.

A phase II study of foretinib in triple-negative, recurrent/metastatic breast cancer: NCIC CTG trial IND.197 (NCT01147484).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1036-1036 ◽  
Author(s):  
Daniel Rayson ◽  
Sasha M. Lupichuk ◽  
Stephen K. L. Chia ◽  
Kylea R. Potvin ◽  
Susan Dent ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Cell Cancer ◽  
Objective Response ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Luminal Breast Cancer ◽  
Egfr Expression ◽  
Grade 3

1036 Background: Met, a receptor tyrosine kinase, is preferentially expressed in basal-like compared to luminal breast cancer. In murine models, overexpression of the oncogenic Met receptor transgene induces tumors with human basal gene expression characteristics supporting Met inhibition as a treatment strategy for triple negative (TN) breast cancer. Foretinib is an oral multi-kinase inhibitor of Met, RON, AXL, TIE-2 and VEGF receptors with anti-tumor activity in advanced HCC and papillary renal cell cancer. Methods: Patients (pts) with TN breast cancer and 0-1 prior regimens for metastatic disease received daily foretinib 60 mg po in a 2-stage single arm trial. Primary endpoints were objective response and early progression rates per RECIST 1.1. Tumor samples were centrally reviewed to confirm ER/PR/HER2 status and for correlative studies including Met, PTEN and EGFR expression. Stage 1 accrual required 23 response-evaluable Met unselected patients with accrual continuing if >/= 1 response or < 17 early progressions (PD <= 8 weeks on study) were observed. Results: Accrual is 29 pts to date; 24 are eligible, 22 evaluable for toxicity and 15 for response. Median age is 56 y (43-81), ECOG PS 0-1 in 23/24. Grade 3 laboratory adverse events were: lymphopenia (9%), elevations in ALT (5%), GGT (5%) and INR (5%). Treatment-related non-hematologic toxicities included (all/grade 3-4) fatigue (64%/5%), nausea (55%/5%), diarrhea (41%/5%), hypertension (32%/14%), vomiting (27%/0%), anorexia (23%/5%) and rash (14%/0%). Three SAEs possibly related to foretinib included; asymptomatic pulmonary embolism, reversible CHF and pleural effusion with QTc prolongation. One PR (7%), 8 early PD (53%) and 6 SD (40%) have been observed to date with median SD duration of 5.4 months (range 2.7-5.5). Preliminary correlative results (IHC): 5/8 (62.5%) evaluable Met positive cases had SD and 4/5 (80%) Met negative cases had PD as best response. Met IHC was negative in the pt with PR. Conclusions: Foretinib shows preliminary evidence of activity and tolerability in metastatic, TN breast cancer. Stage 2 of accrual will include 15 pts with pre-treatment biopsies of metastases and circulating tumor cell collection.

Apatinib plus vinorelbine versus vinorelbine for advanced triple-negative breast cancer with failed first or second-line treatment: The NAN trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1075-1075
Author(s):  
Doudou Li ◽  
Zhonghua Tao ◽  
Biyun Wang ◽  
Leiping Wang ◽  
Jun Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Disease Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Line Treatment ◽  
Second Line ◽  
Grade 3 ◽  
To Receive

1075 Background: No standard treatment exists for triple negative breast cancer (TNBC) with failure of multi-line therapies. Apatinib is a small-molecule tyrosine kinase inhibitor that has promising anti-angiogenesis and antitumor activity for TNBC. We aimed to evaluate the safety and efficacy of adding apatinib to chemotherapy in patients with metastatic TNBC with failed first/second-line treatment. Methods: This randomized, open-label, phase 2 trial recruited patients with advanced TNBC who failed to receive first or second-line treatment. A total of 66 patients were randomly assigned, in a 1:1 ratio, to receive vinorelbine 25 mg/m2 (days 1, 8, 15) or vinorelbine 20 mg/m2 (days 7, 14, 21) with apatinib (250 mg once daily, days 1-5, 8-12, 15-19, if tolerable, the second cycle started with 500 mg per day) in 28-day cycles. The efficacy was evaluated every two treatment cycles (8 weeks ± 3 days). According to the RECIST criterion, patients with CR, PR and SD continued treatment until disease progression or unacceptable toxicity or withdrawal of consent. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response rate (ORR) and safety. Results: Between Sep 14, 2017 and Dec 08, 2020, 66 patients underwent randomization. Median follow-up was 21.3 months. 33 received apatinib plus vinorelbine and 32 received vinorelbine (1 was withdrawal of consent). Median PFS was significantly longer in the apatinib plus vinorelbine group than in the vinorelbine group (3.8 months vs. 1.9 months; hazard ratio for disease progression or death, 1.76; 95% confidence interval [CI], 1.02 to 3.05; P= 0.039). Median OS was 14.6 months with apatinib plus vinorelbine and 14.1 months with vinorelbine (HR,1.34; 95% CI, 0.60 to 3.00; P= 0.469). The ORR was 48.5% in the apatinib plus vinorelbine group and 31.3% in the vinorelbine group ( P= 0.156). The most common treatment-related hematologic grade 3–4 adverse events in those treated with apatinib plus vinorelbine versus vinorelbine, respectively, were leukopenia (42.4% vs. 34.4%), granulocytopenia (57.6% vs. 28.1%), anemia (9.1% vs. 12.5%) and thrombocytopenia (3.1% vs. 3.0%). The most frequent grade 3 nonhematologic toxicities were hand–foot syndrome (21%), proteinuria (9%), hypertension (9%) and increased ALT (9%) and which only occurred in apatinib plus vinorelbine group. No treatment-related nonhematologic grade 4 adverse events or treatment-related deaths were observed. Conclusions: Collectively, among patients with advanced TNBC with failed first/second-line treatment, apatinib plus vinorelbine show a promising benefit in PFS compared to vinorelbine monotherapy. Apatinib plus vinorelbine regimen shows promising efficacy and manageable toxicity, which might be a previously unappreciated therapeutic option for advanced TNBC. Clinical trial information: NCT03254654 .

Preliminary efficacy data of triple-negative breast cancer cohort of NCI 9881 study: A phase II study of cediranib in combination with olaparib in advanced solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1077-1077
Author(s):  
Navid Hafez ◽  
Hatem Hussein Soliman ◽  
Siqing Fu ◽  
Karen A. Gelmon ◽  
Albiruni Ryan Abdul Razak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Objective Response Rate ◽  
Triple Negative ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast

1077 Background: Cediranib, a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, suppresses expression of BRCA1, BRCA2, and RAD51 and increases sensitivity of tumors to poly-(ADP-ribose) polymerase (PARP) inhibitors in vitro. Olaparib, a PARP inhibitor, demonstrates clinical efficacy in patients with germline BRCA1/2 mutations and HER2-negative metastatic breast cancer. We therefore tested the anti-tumor activity of the combination of cediranib and olaparib in patients (pts) with metastatic triple-negative breast cancer (TNBC). Methods: This multi-institutional, two-stage, phase II study enrolled patients with metastatic TNBC previously treated with a minimum of one prior line of systemic therapy in the advanced setting. Patients were treated with cediranib 30mg po daily plus olaparib 200mg po BID until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by RECIST v1.1. Baseline tumor biopsies were obtained for biomarker analyses. Results: Baseline characteristics of the 37pts enrolled are summarized below. The overall objective response rate was 14% (95% CI: 0.025, 0.2453). Median duration of response was 2.0 months (mos) with a range of 1.8 to 6.3 mos. Disease control rate ((# of pts with CR, PR or SD)/(# of evaluable pts)) was 81% (95% CI: 0.6846, 0.937). Median PFS was 3.7 mos (95% CI: 2.1, 4.3). Grade 3/4 adverse events (G3/4 AEs), irrespective of attribution, occurred in 25 of 38 (66%).G3/4 AEs occurring in > 5% of pts were hypertension (24%) and dyspnea (11%), diarrhea (8%) vomiting (8%). Conclusions: The cediranib/olaparib combination resulted in promising objective responses in 14% of biomarker-unselected patients with heavily pre-treated, metastatic TNBC. The regimen required prompt initiation of antihypertensives, but AEs were overall manageable. Analyses of mutation status in homologous recombination DNA repair genes are ongoing and will be correlated with clinical outcome. Clinical trial information: NCT02498613 . [Table: see text]

Phase I/II study of intermitted erlotinib in combination with docetaxel in patients with recurrent non-small cell lung cancer (WJOG4708L)

2019 ◽  
Vol 49 (10) ◽  
pp. 947-955
Author(s):  
Tatsuo Kimura ◽  
Tomoya Kawaguchi ◽  
Yasutaka Chiba ◽  
Hiroshige Yoshioka ◽  
Katsuya Watanabe ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Dose Escalation ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Sequential Administration ◽  
Grade 3

Abstract Background Preclinical data suggest sequential administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) following chemotherapy may improve efficacy. We hypothesized that intermittent delivery of EGFR-TKI following chemotherapy may increase efficacy. Methods This was a multicenter, single-arm phase I/II study to evaluate the efficacy of intermitted erlotinib in combination with docetaxel in patients with EGFR-negative NSCLC who failed one prior chemotherapy. The phase I primary objectives were to determine the maximum tolerated dose (MTD) and recommended dose (RD) of erlotinib. Erlotinib was administered orally once per day on days 2–16 in combination with 60 mg/m2 docetaxel on day1 for 21 days. A standard 3 + 3 dose escalation design was employed for erlotinib from 100 to 150 mg/dose. The phase II primary endpoint was the objective response rate (ORR). The ORR and 95% confidence interval (CI) were calculated using a binomial distribution. This study required 45 patients. Results In the phase I part, the planned dose escalation was completed without reaching MTD. The RD of erlotinib was determined as 150 mg/dose. In the phase II part, the ORR and disease control rate were 17.1% (95%CI: 7.2–32.1%) and 53.7% (95%CI: 37.4–69.3%), respectively. Median progression-free survival and overall survival were 3.5 (95%CI: 3.1–4.5) and 11.3 (95%CI: 8.6–16.6) months, respectively. The common non-hematological adverse event was febrile neutropenia (grade 3–4:19.6%). Two treatment-related deaths were occurred because of interstitial lung disease and pleural infection. Conclusions Intermittent dosing of erlotinib plus docetaxel is clinically feasible in phase I part but did not significantly improve ORR in phase II part.

scholarly journals Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hazem Ghebeh ◽  
Adher Al-Sayed ◽  
Riham Eiada ◽  
Leilani Cabangon ◽  
Dahish Ajarim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Triple Negative ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Skin Lesions ◽  
Weekly Paclitaxel ◽  
Open Label ◽  
Grade 3

AbstractTherapeutic anti-PD-L1 antibodies are safe as a monotherapy, albeit with minimal efficacy in triple-negative breast cancer (TNBC). This trial aimed to test the safety and efficacy of Durvalumab and Paclitaxel in metastatic TNBC. In this open-label, one-arm trial, five cycles of weekly paclitaxel were delivered intravenously (IV) concurrent with Durvalumab that was given IV every 2 weeks. The combination was preceded by one cycle of paclitaxel alone, for immunological priming, followed by Durvalumab solo until disease progression or unacceptable toxicity. Between 2017 and 2019, 14 patients received at least one cycle of the combination therapy. The therapy was safe with no-dose limiting toxicity, except one case of skin lesions. Adverse events (AEs) were reported in 71% of patients, and there was no death due to the combination therapy. Regardless of grade, the most common AEs were headache and peripheral neuropathy, as each happened in four patients (29%), followed by fatigue and skin rash in three patients (21%) each. Grade 3/4 AEs were experienced by three patients (21%), with the most common being headache and anemia, which happened in two patients (14%). The confirmed objective response rate (ORR) was observed in five patients with a median duration of 10.0 months. Median Progression-free survival (PFS) and overall survival (OS) were 5 and 20.7 months, respectively. The combination of Durvalumab and Paclitaxel is safe, leaving room for additional agents. This is the first report on the combination of Durvalumab and Paclitaxel in the treatment of TNBC (NCT02628132).

Immediate and long-term results of the first line chemotherapy in patients with metastatic triple negative breast cancer. Final analysis of randomized study

2020 ◽  
pp. 75-80
Author(s):  
S.A. Lyalkin ◽  
◽  
L.A. Syvak ◽  
N.O. Verevkina ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Randomized Study ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Group 2 ◽  
Line Chemotherapy ◽  
Group 1

The objective: was to evaluate the efficacy of the first line chemotherapy in patients with metastatic triple negative breast cancer (TNBC). Materials and methods. Open randomized study was performed including 122 patients with metastatic TNBC. The efficacy and safety of the first line chemotherapy of regimens АТ (n=59) – group 1, patients received doxorubicine 60 мг/м2 and paclitaxel 175 мг/м2 and ТР (n=63) – group 2, patients received paclitaxel 175 мг/м2 and carboplatin AUC 5 were evaluated. Results. The median duration of response was 9.5 months (4.5–13.25 months) in patients received AT regimen and 8.5 months (4.7–12.25 months), in TP regimen; no statistically significant differences were observed, р=0.836. The median progression free survival was 7 months (95% CI 5–26 months) in group 1 and 7.5 months (95% CI 6–35 months) in group 2, p=0.85. Both chemotherapy regimens (AT and TP) had mild or moderate toxicity profiles (grade 1 or 2 in most patients). No significant difference in gastrointestinal toxicity was observed. The incidence of grade 3–4 neutropenia was higher in patients of group 2 (TP regimen): 42.8% versus 27% (р<0.05). Conclusions. Both regimens of chemotherapy (AT and TP) are appropriate to use in the first line setting in patients with metastatic TNBC. Key words: metastatic triple negative breast cancer, chemotherapy, progression free survival, chemotherapy toxicity.

Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

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