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Clinical Trial
. 2024 Sep 20;42(27):3207-3217.
doi: 10.1200/JCO.23.02010. Epub 2024 Aug 5.

Trastuzumab Deruxtecan in Human Epidermal Growth Factor Receptor 2-Expressing Biliary Tract Cancer (HERB; NCCH1805): A Multicenter, Single-Arm, Phase II Trial

Akihiro Ohba  1 , Chigusa Morizane  1 , Yasuyuki Kawamoto  2 , Yoshito Komatsu  2 , Makoto Ueno  3 , Satoshi Kobayashi  3 , Masafumi Ikeda  4 , Mitsuhito Sasaki  4 , Junji Furuse  3   5 , Naohiro Okano  5 , Nobuyoshi Hiraoka  6 , Hiroshi Yoshida  6 , Aya Kuchiba  7 , Ryo Sadachi  7 , Kenichi Nakamura  8 , Naoko Matsui  8 , Yoshiaki Nakamura  9 , Wataru Okamoto  10 , Takayuki Yoshino  9 , Takuji Okusaka  1
Affiliations
Clinical Trial

Trastuzumab Deruxtecan in Human Epidermal Growth Factor Receptor 2-Expressing Biliary Tract Cancer (HERB; NCCH1805): A Multicenter, Single-Arm, Phase II Trial

Akihiro Ohba et al. J Clin Oncol. .

Abstract

Purpose: Treatment options for patients with unresectable or recurrent biliary tract cancer (BTC) who progress on a gemcitabine-containing regimen are limited. In addition, the significance of anti-human epidermal growth factor receptor 2 (HER2) therapy in HER2-expressing BTC has not been sufficiently investigated.

Methods: In this phase II trial, participants from five institutions in Japan were enrolled. Eligible patients had pathologically confirmed unresectable or recurrent BTC with centrally confirmed HER2-positive (immunohistochemistry [IHC]3+ or IHC2+ and in situ hybridization [ISH]+) or HER2-low (IHC2+ and ISH-, IHC1+, and IHC0 and ISH+) and were refractory or intolerant to a gemcitabine-containing regimen. The patients received 5.4 mg/kg trastuzumab deruxtecan (T-DXd) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was the confirmed objective response rate (ORR) in HER2-positive BTC by an independent central review (threshold ORR, 15%; expected ORR, 40%).

Results: A total of 32 patients were enrolled and treated. Among these patients, 22 with HER2-positive disease comprised the primary efficacy population and had a confirmed ORR of 36.4% (90% CI, 19.6 to 56.1; P = .01), meeting the primary end point. Eight with HER2-low disease comprised the exploratory population and had a confirmed ORR of 12.5%. The most common ≥grade 3 treatment-related adverse events were anemia (53.1%) and neutropenia (31.3%). Eight patients (25.0%) had interstitial lung disease (ILD), including two grade 5 events.

Conclusion: T-DXd showed promising activity in patients with HER2-positive BTC and a signal of efficacy in patients with HER2-low BTC. Although the safety profile was generally manageable, ILD requires careful monitoring and early intervention.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Figures

FIG 1.
FIG 1.
Study flow diagram. BTC, biliary tract cancer; HAHA, human antihuman antibody; HER2, human epidermal growth factor receptor 2; PK, pharmacokinetic. aThe patient was administered systemic steroid therapy ≤14 days before enrollment. bThe patient had pulmonary fibrosis on imaging at screening.
FIG 2.
FIG 2.
Tumor shrinkage and response durability. (A) Waterfall plots of maximum tumor shrinkage from the baseline by BICR among HER2-positive and HER2-low patients. (B) Duration of response in HER2-positive patients who responded to study treatment by LIR. (C) Spider plots of tumor shrinkage at each time point by LIR among HER2-positive and HER2-low patients. BICR, blinded independent central review; CR, complete response; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization; LIR, local investigator review; NE, not evaluable; PD, progressive disease; PR, partial response; SD, stable disease.
FIG 3.
FIG 3.
PFS and OS. (A) PFS by LIR among HER2-positive patients. (B) PFS by LIR among HER2-low patients. (C) OS among HER2-positive patients. (D) OS among HER2-low patients. HER2, human epidermal growth factor receptor 2; LIR, local investigator review; OS, overall survival; PFS, progression-free survival.
FIG A1.
FIG A1.
Waterfall plots by HER2 status of maximum tumor shrinkage from baseline by BICR among (A) HER2-positive and (B) HER2-low. BICR, blinded independent central review; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization.
FIG A2.
FIG A2.
PK profile in PK/HAHA analysis set (n = 7). HAHA, human anti-human antibody; HER2, human epidermal growth factor receptor 2; PK, pharmacokinetic.
See this image and copyright information in PMC

References

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