Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2‐positive breast cancer: An open‐label, dose‐escalation, phase I study

3076 Background: HM781-36B is a pan-HER tyrosine kinase inhibitor, which showed a potent activity against the gefitinib- or erlotinib-resistant, EGFR L858R/T790M double mutant cells. A phase I study was conducted to determine the MTD, pharmacokinetics, and antitumor activity. Methods: Eligible pts had advanced malignancies refractory to standard therapies. Standard 3+3 scheme was used in the dose escalation part, and additional 12 pts were enrolled in the expansion cohort of molecular enrichment. Results: In dose-escalation part, 43 pts (median age: 55 yrs (range 25-82), M:F=25:18, ECOG PS 0/1/2/3: 23/17/2/1, median prior chemotherapy: 4) were treated. DLTs were G3 diarrheas in 5 pts, one at 12 mg, 16 mg, 24 mg, and two at 32 mg. The MTD was determined as 24mg. The most common drug-related adverse events were diarrhea, stomatitis, rash, pruritus, and anorexia. Among 41 evaluable pts, 4 pts achieved PR (1 unconfirmed, duration of response: 11.9 mo, 7.07 mo+, 4.5 mo+), and 19 pts had SD. Two of 4 PR pts were Her2-positive breast cancer pts. The median duration of treatment in pts with PR or SD was 3.87 (2.47- 15.17) months. In the dose range of 0.5 to 24 mg, it showed linear pharmacokinetics proportional to dose-escalation, relatively short half-life, and little accumulation. Additional 12 pts in the expansion cohort are under treatment at 24 mg (6 pts: EGFR-mutant NSCLC, 3 pts: Her2-positive gastric cancer, 2 pts: Her2-positive breast cancer, 1 pt: rectal cancer). Conclusions: HM781-36B was safe and well tolerable in advanced solid tumors. Preliminary evidence of anticancer activity has been observed. Updated data will be presented at the meeting.

Download Full-text

Abstract PS10-51: TAA013 a trastuzumab antibody drug conjugate phase I dose escalation study in recurrent her2 positive breast cancer

10.1158/1538-7445.sabcs20-ps10-51 ◽

2021 ◽

Author(s):

J M Liu ◽

Y M Yin ◽

Hao Wu ◽

W Li ◽

X Huang ◽

...

Keyword(s):

Breast Cancer ◽

Phase I ◽

Dose Escalation ◽

Antibody Drug Conjugate ◽

Her2 Positive ◽

Dose Escalation Study ◽

Drug Conjugate ◽

Her2 Positive Breast Cancer ◽

Antibody Drug ◽

Positive Breast Cancer

Download Full-text

Phase I study of lapatinib (L) in combination with whole-brain radiation therapy (WBRT) in patients (pts) with brain metastases from HER2-positive breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.1154 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 1154-1154 ◽

Cited By ~ 6

Author(s):

N. U. Lin ◽

N. Ramakrishna ◽

W. J. Younger ◽

A. M. Storniolo ◽

S. E. Come ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Brain Metastases ◽

Phase I ◽

Phase I Study ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Whole Brain Radiation ◽

Brain Radiation ◽

Positive Breast Cancer

Download Full-text

A phase I dose-escalation study evaluating weekly paclitaxel with neratinib and trastuzumab in women with metastatic HER2-positive breast cancer, NSABP FB-8.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.611 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 611-611 ◽

Cited By ~ 6

Author(s):

Rachel Catherine Jankowitz ◽

Jame Abraham ◽

Antoinette R. Tan ◽

Steven A. Limentani ◽

Laura M Adamson ◽

...

Keyword(s):

Breast Cancer ◽

Phase I ◽

Dose Escalation ◽

Weekly Paclitaxel ◽

Erbb Receptors ◽

Her2 Positive ◽

Dose Escalation Study ◽

Cancer Trial ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

611 Background: Dual blockade of ErbB receptors combined with chemotherapy compared with single-agent blockade improves efficacy in HER2-positive disease. FB-8 is single arm, Phase I dose-escalation study to determine safety and tolerability of weekly paclitaxel (P), the irreversible tyrosine kinase inhibitor, neratinib (N) and trastuzumab (T) in women with metastatic, HER2-positive breast cancer (MBC). Methods: Women with measurable or non-measurable MBC (ECOG PS 0 - 2) received P (80 mg/m2 IV days 1, 8, 15 of 28-day cycle), T (4 mg/kg IV, then 2 mg/kg IV weekly), and N (oral, daily). N was dose-escalated using 3+3 design at 120 mg, 160 mg, and 240 mg, dose-limiting toxicity (DLT) determined in cycle 1. All patients (pts) received prophylactic anti-diarrheals. Results: All pts were taxane and trastuzumab pre-treated, with mean of 4 prior regimens. At N=120 mg, there was 1 DLT, grade (gr) 3 diarrhea with dehydration. Three more pts were enrolled; none experienced DLT. At N=160 mg, there were no DLTs. At N=240 mg, 2 of 3 pts had DLTs: one gr 3 diarrhea and dehydration, one gr 3 diarrhea, dehydration, and gr 3 mucositis. After de-escalation to N=160 mg, 3 more pts were added. If N=160 mg is well tolerated, a 200 mg cohort is planned. 12 pts completed cycle 1. Efficacy data are available on 10: CR 1, PR 3, SD 1 (8+months). One pt* had resolution of non-target disease (skin and breast mass). 4 pts were off-study before the first scan (DLT 3 and progressive disease 1) and are considered non-responders (NR). The most frequent grade 3-4 adverse event was diarrhea, 3 pts. Conclusions: Dual anti-HER blockade with N, T combined with P is tolerable and highly active in pts pre-treated with anti-HER2 agents and chemotherapy. This combination will be studied in a phase II neoadjuvant breast cancer trial (NSABP FB-7). We thank Pfizer, Inc and Puma Biotechnology, Inc for their support. [Table: see text]

Download Full-text