Multicenter Phase II study to evaluate efficacy and safety of combination therapy with trastuzumab and pertuzumab in patients with HER2-positive metastatic colorectal cancer

Conditions

colorectal cancer

Kobayashi S, Bando H, Taketomi A, Takamoto T, Shinozaki E, Shiozawa M, Hara H, Yamazaki K, Komori K, Matsuhashi N, Kato T, Kagawa Y, Yokota M, Oki E, Komine K, Takahashi S, Wakabayashi M, Yoshino T.

2023-08-214 citations

10.1186/s12885-023-11311-5

Trajectory for the Regulatory Approval of a Combination of Pertuzumab Plus Trastuzumab for Pre-treated HER2-positive Metastatic Colorectal Cancer Using Real-world Data.

Sakamoto Y, Bando H, Nakamura Y, Hasegawa H, Kuwaki T, Okamoto W, Taniguchi H, Aoyagi Y, Miki I, Uchigata H, Kuramoto N, Fuse N, Yoshino T, Ohtsu A.

2022-10-228 citations

10.1016/j.clcc.2022.10.003

Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial.

Nakamura Y, Okamoto W, Kato T, Esaki T, Kato K, Komatsu Y, Yuki S, Masuishi T, Nishina T, Ebi H, Sawada K, Taniguchi H, Fuse N, Nomura S, Fukui M, Matsuda S, Sakamoto Y, Uchigata H, Kitajima K, Kuramoto N, Asakawa T, Olsen S, Odegaard JI, Sato A, Fujii S, Ohtsu A, Yoshino T.

2021-11-11171 citations

10.1038/s41591-021-01553-w

Pertuzumab plus trastuzumab and real-world standard of care (SOC) for patients (pts) with treatment refractory metastatic colorectal cancer (mCRC) with <i>HER2</i> (<i>ERBB2</i>) amplification (amp) confirmed by tumor tissue or ctDNA analysis (TRIUMPH, EPOC1602).

Wataru Okamoto, Yoshiaki Nakamura, Takeshi Kato, Taito Esaki, Masato Komoda et al. (20 authors)

Journal of Clinical Oncology2021-05-2012 citations

10.1200/jco.2021.39.15_suppl.3555

Interventions

Combination therapy with trastuzumab and pertuzumab 1) Trastuzumab: 8 mg/kg (first dose), 6 mg/kg (second and subsequent doses), every 3 weeks 2) Pertuzumab: 840 mg (first dose), 420 mg (second an

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Patients who meet both the eligibility criteria A and B will be enrolled in the study treatment group. Patients who meet the eligibility criteria A but do not meet the eligibility criteria B will be enrolled in the natural history follow-up group. Eligibility criteria A: 1)Age 20 years or above 2)Has metastatic colorectal cancer that is histologically diagnosed as adenocarcinoma 3)Has cancer with wild-type KRAS codons 12 and 13 in tumor tissue. If KRAS codons 59, 61, 117, and 146 and NRAS codons 12, 13, 59, 61, 117, and 146 are also analyzed, the statuses for all these RAS codons must be wild type. 4)Meet the following (1) or (2) (1)Has cancer that meets either of the following based on central assessment with HER2 IHC and HER2 FISH - IHC3+ - FISH positive (HER2/CEP17 ratio >= 2.0) (2) Has cancer that is diagnosed with both of the following based on central assessment with liquid biopsy - HER2 amplified ('++' or '+++' on the qualitative scale) and RAS wild-type 5)Refractory or intolerant to fluoropyrimidine oxaliplatin, irinotecan, cetuximab, or panitumumab 6)Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 7)Has a life expectancy of at least 12 weeks 8)Be able to provide written informed consent Eligibility criteria B: 1) Has never been treated with HER2-targeted drugs 2) Has a measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 3)Is not breast-feeding 4)Is willing to use appropriate contraception 5)Has no history of other malignancies within 3 years before the start of the study treatment 6)Has not undergone another antitumor treatment concurrently 7)Has not undergone major surgery within 4 weeks before the start of study treatment 8)Has serious, clinically significant abnormalities that are acute or chronic 9)Is willing to receive the study treatment

Exclusion criteria

Exclusion criteria: 1)Has a known history of bone marrow transplantation or organ transplantation 2)Has a positive result on the serum pregnancy test 3)Is judged by the investigator to be inappropriate for study participation for any reason.

Design outcomes

Primary

Measure	Time frame
Confirmed objective response rate (ORR) by investigators' assessment	—

Secondary

Measure	Time frame
- Progression-free survival (PFS) - Duration of response (DoR) - Time to treatment failure (TTF) - Disease control rate (DCR) - Overall survival (OS) - Confirmed ORR by central assessment - Incidences of adverse events - ORR and PFS in the previous regimens containing an anti-EGFR monoclonal antibody (cetuximab or panitumumab)	—

Countries

Japan

Contacts

Public ContactYoshiaki Nakamura

National Cancer Center Hospital East Department of Gastrointestinal Oncology

triumph_core@east.ncc.go.jp04-7133-1111

Outcome results

None listed