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TRIUMPH: Primary Efficacy of a Phase II Trial of Trastuzumab (T) and Pertuzumab (P) in Patients (pts) with Metastatic Colorectal Cancer (mCRC) with HER2 (ERBB2) Amplification (amp) in Tumor Tissue or Circulating Tumor DNA (ctDNA): A GOZILA Sub-study

Date

29 Sep 2019

Session

Poster Discussion – Gastrointestinal tumours, colorectal

Presenters

Yoshiaki Nakamura

Citation

Annals of Oncology (2019) 30 (suppl_5): v198-v252. 10.1093/annonc/mdz246

Authors

Y. Nakamura1, W. Okamoto2, T. Kato3, H. Hasegawa4, K. Kato5, S. Iwasa6, T. Esaki7, Y. Komatsu8, T. Masuishi9, T. Nishina10, S. Nomura11, M. Fukui11, S. Matsuda11, A. Sato11, S. Fujii12, J.I. Odegaard13, S. Olsen14, T. Yoshino1

Author affiliations

  • 1 Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 2 Cancer Treatment Center, Hiroshima University Hospital, 7348551 - Hiroshima/JP
  • 3 Department Of Surgery, Osaka National Hospital, 5400006 - Osaka/JP
  • 4 Department Of Gastroenterology And Hepatology, Osaka National Hospital, 5400006 - Osaka/JP
  • 5 Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo/JP
  • 6 Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 1040045 - Tokyo/JP
  • 7 Department Of Gastrointestinal And Medical Oncology, National Kyushu Cancer Center, 8111395 - Fukuoka/JP
  • 8 Department Of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, 0608648 - Sapporo/JP
  • 9 Department Of Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 10 Department Of Gastrointestinal Medical Oncology, Shikoku Cancer Center, 791-0280 - Matsuyama/JP
  • 11 Clinical Research Support Office, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 12 Division Of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 277-8577 - Kashiwa/JP
  • 13 Clinical Development, Guardant Health, 94063 - Redwood City/US
  • 14 Clinical And Medical Affairs, Guardant AMEA, 1050021 - Tokyo/JP
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Background

ERBB2 amp occurs in approximately 4% of pts with mCRC. We conducted a phase II trial to evaluate the efficacy and safety of T and P in pts with ERBB2-amplified mCRC identified by tissue and/or ctDNA analysis.

Methods

We enrolled pts with central tissue and/or ctDNA (Guardant360) confirmed wild-type RAS and ERBB2-amplified mCRC, refractory or intolerant to standard chemotherapy including EGFR blockade. Pts received T and P every 3 weeks. The primary endpoint was confirmed objective response rate (ORR) by investigator assessment, analyzed for two primary populations: tissue-positive and ctDNA-positive. The required sample size for each group was 25 (one-sided α = 2.5%, β = 10%) to test the threshold ORR of 5% against the expected ORR of 30%; 5 confirmed responses were needed to determine statistical significance.

Results

The first response evaluation was done on Jan 7, 2019. Of 19 pts enrolled at 7 sites, 18 were evaluable for response. ERBB2-amp was confirmed in both tissue and ctDNA for 14 pts, in tissue alone for 3, and in ctDNA alone for 1; therefore, 17 and 15 pts were assigned to the tissue-positive and the ctDNA-positive group, respectively. With median follow-up of 5.4 months, there were 6 confirmed responders in the tissue-positive group (ORR = 35%, 95% confidence interval [CI] 14-62%; 1 CR and 5 PR) and 5 in the ctDNA positive group (ORR = 33%, 95% CI 12-62%; 1 CR and 4 PR). Median progression-free survival for both groups was 4.0 months (95% CI = 1.4-5.6 months and 1.3-5.6 months, respectively). Clonal ctDNA mutations in KRAS, BRAF, PIK3CA, or ERBB2 at baseline were observed only in pts with disease progression as best response. The safety profile of T and P was consistent with prior reports. Severe adverse events were reported in 2 pts: Gr 3 decreased ejection fraction and Gr 3 infusion related reaction.

Conclusions

The TRIUMPH study met its primary endpoint, demonstrating that combination of T and P has promising activity, with an acceptable toxicity profile, in treatment-refractory mCRC pts with ERBB2 amp in tissue and/or ctDNA. Clonal oncogenic ctDNA driver mutations may predict for primary resistance.

Clinical trial identification

UMIN000027887.

Editorial acknowledgement

Legal entity responsible for the study

SCRUM-Japan GI-SCREEN.

Funding

Japan Agency for Medical Research and Development.

Disclosure

Y. Nakamura: Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Ono Pharmaceutical. W. Okamoto: Research grant / Funding (self): MSD. T. Kato: Honoraria (self), Research grant / Funding (self): Chugai Pharma; Honoraria (self): Takeda; Honoraria (self): Bayer; Honoraria (self): Lilly; Honoraria (self): Yakult Honsha; Honoraria (self): Sanofi. K. Kato: Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Advisory / Consultancy: MSD; Advisory / Consultancy: Oncolys BioPharma; Research grant / Funding (self): Shionogi; Research grant / Funding (self): MSD Oncology. S. Iwasa: Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Ono Pharmaceutical; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Bayer. T. Esaki: Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): Eisai; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self): Takeda; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): Sanofi; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Nihonkayaku; Research grant / Funding (institution): Pfizer. Y. Komatsu: Speaker Bureau / Expert testimony, Research grant / Funding (self): Taiho Pharmaceutical; Speaker Bureau / Expert testimony, Research grant / Funding (self): Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self): Chugai Pharma; Speaker Bureau / Expert testimony: Merck Serono; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Novartis; Honoraria (self), Speaker Bureau / Expert testimony: Pfizer; Honoraria (institution), Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Speaker Bureau / Expert testimony, Research grant / Funding (self): Ono Pharmaceutical; Speaker Bureau / Expert testimony: Yakult Honsha; Speaker Bureau / Expert testimony, Research grant / Funding (self): Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi; Speaker Bureau / Expert testimony: Bristol-Myers Squibb Japan; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: TOWA; Speaker Bureau / Expert testimony: Nipro Corporation; Research grant / Funding (self): MSD; Research grant / Funding (self): Yakult Pharmaceutical; Research grant / Funding (self): Sumitomo Dainippon Pharma; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Sysmex. T. Masuishi: Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Merck Serono; Honoraria (self): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Yakult Honsha; Honoraria (self): Takeda; Honoraria (self): Lilly; Honoraria (self): Bayer Yakuhin; Honoraria (self): Sanofi. T. Nishina: Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Lilly; Research grant / Funding (institution): Lilly Japan; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Takeda; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Nihonkayaku; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Ono Pharmaceutical. J.I. Odegaard: Shareholder / Stockholder / Stock options, Full / Part-time employment: Guardant Health. S. Olsen: Full / Part-time employment: Guardant Health AMEA; Shareholder / Stockholder / Stock options: Guardant Health; Shareholder / Stockholder / Stock options: AstraZeneca. T. Yoshino: Research grant / Funding (institution): Sumitomo Dainippon Pharma Co., Ltd.; Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Research grant / Funding (institution): Sanofi. K.K.; Research grant / Funding (institution): Daiichi Sankyo Company, Limited; Research grant / Funding (institution): Parexel International Inc.; Research grant / Funding (institution): Ono Pharmaceutical Co., Ltd.; Research grant / Funding (institution): MSD. K. K. All other authors have declared no conflicts of interest.

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