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Status unknownNCT03698383Updated Feb 18, 2021

Phase II Study of Herzuma® Plus Gedatolisib in Patients With HER-2 Positive Metastatic Breast Cancer

A Phase 2 interventional study of Trastuzumab biosimilars(Herzuma), Gedatolisib in HER2-positive Breast Cancer and Metastatic Breast Cancer, sponsored by Korean Cancer Study Group. Status unknown at 1 site in Korea, Republic of. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2021-02-18.

Sponsored by Korean Cancer Study Group · Phase 2, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Feb 2021), so the status shown — last known as Recruiting — may be out of date.
Phase
Phase 2
Study type
Interventional
Enrollment
15
Allocation
Not applicable
Ages
19 Years and older
Sex
All
01

Study summary

Phase II Pilot Study of Trastuzumab Biosimilar (Herzuma®) plus Gedatolisib in Patients with HER-2 Positive Metastatic Breast Cancer Who Progressed after 2 or more HER-2 directed Chemotherapy

Read the detailed description

All the patients will be included in the final analysis, with a total of 15 patients to be enrolled.

Treatment will occur until disease progression, unacceptable toxicity or patient withdrawal.

Tumor measurement and evaluation are going to be performed at every 6 weeks for the first 3 months, then at every 9 weeks till progression, and then follow-up evaluation at every 12 weeks thereafter end of study.

02

Conditions studied

  • HER2-positive Breast Cancer
  • Metastatic Breast Cancer

Browse trials for

Keywords

  • Herzuma
  • Gedatolisib
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's planned enrollment of 15 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Korean Cancer Study Group is the lead sponsor of 9 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
19 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Breast tumor with suspected PI3K-pathway dependence (either by mutation or by known biologic rationale. PI3K dependence includes the presence of a PIK3CA-mutant hotspot mutation, PIK3CA copy number gain, mTOR hotspot mutation, or PTEN loss in the archival or fresh tumor tissue specimen identified in K-MASTER panel. All genetic findings must be reviewed by the study PI, prior to study entry.).
  • Patient is an adult, female ≥ 19 years old at the time of informed consent.
  • Patient has histologically and/or cytologically confirmed diagnosis of HER2-positive breast cancer. HER2-positive breast cancer as defined by an immunohistochemistry (IHC) score of 3+ or gene amplified by in situ hybridization (ISH) as defined by a ratio of ≥ 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies.Metastatic or unresectable disease documented on diagnostic imaging studies.
  • Metastatic or unresectable disease documented on diagnostic imaging studies.
  • Prior 2 or more HER-2 directed therapy including trastuzumab for metastatic disease is mandatory.
  • Patient must have at least one measurable lesion according to Response valuation Criteria in Solid Tumors version 1.1 (RECIST v.1.1).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
  • Adequate bone marrow and organ function including: WBC ≥ 3500/mL; Platelets ≥ 100,000/uL; Hemoglobin >9.0 g/dL; Total bilirubin ≤ 1.5x ULN; AST and ALT \< 2.5 x ULN; Alkaline phosphatase \<2.5x ULN; Creatinine ≤ 1.5x ULN or CCr >60 ml/min for patients with abnormal serum Cr level function.
  • Adequate glucose control, as defined by HbA1c \< 7% and fasting blood glucose ≤ 126 mg/dL (7.0 mmoL/L).
  • Adequate glucose control, as defined by HbA1c \< 7% and fasting blood glucose ≤ 126 mg/dL (7.0 mmoL/L).
  • Life expectancy higher than 3 months
  • Patient has an adequate left ventricular ejection function of at least 50 % at baseline, as measured by echocardiography.
  • Written informed consent

Exclusion criteria

Exclusion Criteria:

  • Patient is pregnant or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
  • Patient has received previous treatment with a mechanistic target of rapamycin (mTOR) inhibitor or phosphoinositide 3-kinase (PI3K) inhibitor.
  • Patient has symptomatic and unstable CNS metastases, except for treated brain metastases. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed.
  • Active and clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus syndrome (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. Baseline viral assessment is not required in patients with no known infection.
  • Current use or anticipated need for food or medications that are known moderate or greater CYP3A4 inhibitors, including their administration within 7-days prior to the first gedatolisib dose and while receiving investigational product (ie, strong CYP3A4 inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits [e.g., Seville oranges, pomelos], ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, troleandomycin, mibefradil, conivaptan; moderate CYP3A4 inhibitors: erythromycin, verapamil, atazanavir, delavirdine, fluconazole, darunavir, diltiazem, aprepitant, imatinib, tofisopam, ciprofloxacin, and cimetidine).
  • Concurrent use or anticipated need for medications that are mainly metabolized by UGT1A9 including their administration within 7-days prior to the first dose of investigational product (e.g., propofol, propranolol, dapagliflozin, darexaban, mycophenolic acid, and tapentadol).
  • Acetaminophen use within 24 hours before or after the first dose of gedatolisib.
  • Current use or anticipated need for food or medications that are metabolized by CYP2D6, and of narrow therapeutic index including their administration within 10-days prior to the first gedatolisib dose and while receiving investigational product.
  • Concurrent use of herbal preparations.
  • Major surgery within 4 weeks of first dose of investigational product or not fully recovered from any side effects of previous procedures.
  • Any other malignancy within 3 years prior to first dose of investigational product except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
  • QTc interval >480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
  • Any of the following within 6 months of first dose of investigational product myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE v. 5.0 Grade ≤2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
  • History of interstitial pneumonitis.
  • Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
15 participants (estimated)

Study arms

  • Experimental
    Herzuma plus Gedatolisib

    Drug: Trastuzumab biosimilars(Herzuma), Gedatolisib

Interventions

  • DrugTrastuzumab biosimilars(Herzuma), Gedatolisib

    * Trastuzumab biosimilar: Intravenously administered on Day 1 of every 21 day cycle at a dose of 6mg/kg (loading dose 8mg/kg at 1C) * Gedatolisib: Intravenously administered on Day 1, 8 and 15 of every 21 day cycle at a dose of 180mg

    Also known as: Herzuma plus Gedatolisib

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What researchers measure

Primary outcomes

  1. Objective response rate

    the percentage of patients experiencing confirmed complete response (CR) and partial response (PR) assessed by RECIST criteria v.1.1

    Time frame: within maximum 3 years

Secondary outcomes

  1. Progression free survival

    the time from study entry until the first observation of disease progression according to the above schedule or death due to any cause

    Time frame: within maximum 3 years

  2. Overall survival

    the time from study entry until death

    Time frame: within maximum 3 years

07

Study locations

1 of 1 sites recruiting
  • Samsung Medical Center
    Seoul, Korea, Republic of
    • Yeon Hee Park, MD, PhD · Contact
    Recruiting
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References and documents

Publications

  • Harbeck N, Huang CS, Hurvitz S, Yeh DC, Shao Z, Im SA, Jung KH, Shen K, Ro J, Jassem J, Zhang Q, Im YH, Wojtukiewicz M, Sun Q, Chen SC, Goeldner RG, Uttenreuther-Fischer M, Xu B, Piccart-Gebhart M; LUX-Breast 1 study group. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):357-366. doi: 10.1016/S1470-2045(15)00540-9. Epub 2016 Jan 26. PubMed 26822398 ↗
  • Wong HH, Collins J, McAdam K, Wilson C. Trastuzumab beyond progression in advanced breast cancer: national guidance versus oncologist's decision. Oncology. 2014;86(1):22-3. doi: 10.1159/000356876. Epub 2013 Dec 10. No abstract available. PubMed 24335099 ↗
  • Rexer BN, Arteaga CL. Optimal targeting of HER2-PI3K signaling in breast cancer: mechanistic insights and clinical implications. Cancer Res. 2013 Jul 1;73(13):3817-20. doi: 10.1158/0008-5472.CAN-13-0687. Epub 2013 Jun 21. PubMed 23794708 ↗
  • Wang L, Yu X, Wang C, Pan S, Liang B, Zhang Y, Chong X, Meng Y, Dong J, Zhao Y, Yang Y, Wang H, Gao J, Wei H, Zhao J, Wang H, Hu C, Xiao W, Li B. The anti-ErbB2 antibody H2-18 and the pan-PI3K inhibitor GDC-0941 effectively inhibit trastuzumab-resistant ErbB2-overexpressing breast cancer. Oncotarget. 2017 May 16;8(32):52877-52888. doi: 10.18632/oncotarget.17907. eCollection 2017 Aug 8. PubMed 28881779 ↗
  • Courtney KD, Corcoran RB, Engelman JA. The PI3K pathway as drug target in human cancer. J Clin Oncol. 2010 Feb 20;28(6):1075-83. doi: 10.1200/JCO.2009.25.3641. Epub 2010 Jan 19. PubMed 20085938 ↗
  • Del Campo JM, Birrer M, Davis C, Fujiwara K, Gollerkeri A, Gore M, Houk B, Lau S, Poveda A, Gonzalez-Martin A, Muller C, Muro K, Pierce K, Suzuki M, Vermette J, Oza A. A randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer. Gynecol Oncol. 2016 Jul;142(1):62-69. doi: 10.1016/j.ygyno.2016.04.019. Epub 2016 Apr 24. PubMed 27103175 ↗
  • Janku F, Wheler JJ, Naing A, Falchook GS, Hong DS, Stepanek VM, Fu S, Piha-Paul SA, Lee JJ, Luthra R, Tsimberidou AM, Kurzrock R. PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res. 2013 Jan 1;73(1):276-84. doi: 10.1158/0008-5472.CAN-12-1726. Epub 2012 Oct 12. PubMed 23066039 ↗
  • Baselga J, Cortes J, Im SA, Clark E, Ross G, Kiermaier A, Swain SM. Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. J Clin Oncol. 2014 Nov 20;32(33):3753-61. doi: 10.1200/JCO.2013.54.5384. Epub 2014 Oct 20. PubMed 25332247 ↗
  • Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, Tseng LM, Zhang Q, Shen K, Liu D, Dreosti LM, Burris HA, Toi M, Buyse ME, Cabaribere D, Lindsay MA, Rao S, Pacaud LB, Taran T, Slamon D. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015 Jul;16(7):816-29. doi: 10.1016/S1470-2045(15)00051-0. Epub 2015 Jun 16. PubMed 26092818 ↗
  • Andre F, Hurvitz S, Fasolo A, Tseng LM, Jerusalem G, Wilks S, O'Regan R, Isaacs C, Toi M, Burris H, He W, Robinson D, Riester M, Taran T, Chen D, Slamon D. Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3. J Clin Oncol. 2016 Jun 20;34(18):2115-24. doi: 10.1200/JCO.2015.63.9161. Epub 2016 Apr 18. Erratum In: J Clin Oncol. 2019 Feb 1;37(4):357. doi: 10.1200/JCO.18.02261. PubMed 27091708 ↗
  • Mauro C, Smith J, Cucchi D, Coe D, Fu H, Bonacina F, Baragetti A, Cermenati G, Caruso D, Mitro N, Catapano AL, Ammirati E, Longhi MP, Okkenhaug K, Norata GD, Marelli-Berg FM. Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110delta-Akt-Mediated Signals. Cell Metab. 2017 Mar 7;25(3):593-609. doi: 10.1016/j.cmet.2017.01.008. Epub 2017 Feb 9. PubMed 28190771 ↗
  • Roychoudhuri R, Eil RL, Restifo NP. The interplay of effector and regulatory T cells in cancer. Curr Opin Immunol. 2015 Apr;33:101-11. doi: 10.1016/j.coi.2015.02.003. Epub 2015 Feb 27. PubMed 25728990 ↗
  • Patton DT, Wilson MD, Rowan WC, Soond DR, Okkenhaug K. The PI3K p110delta regulates expression of CD38 on regulatory T cells. PLoS One. 2011 Mar 1;6(3):e17359. doi: 10.1371/journal.pone.0017359. PubMed 21390257 ↗
  • Pearce VQ, Bouabe H, MacQueen AR, Carbonaro V, Okkenhaug K. PI3Kdelta Regulates the Magnitude of CD8+ T Cell Responses after Challenge with Listeria monocytogenes. J Immunol. 2015 Oct 1;195(7):3206-17. doi: 10.4049/jimmunol.1501227. Epub 2015 Aug 26. PubMed 26311905 ↗
  • Crompton JG, Sukumar M, Roychoudhuri R, Clever D, Gros A, Eil RL, Tran E, Hanada K, Yu Z, Palmer DC, Kerkar SP, Michalek RD, Upham T, Leonardi A, Acquavella N, Wang E, Marincola FM, Gattinoni L, Muranski P, Sundrud MS, Klebanoff CA, Rosenberg SA, Fearon DT, Restifo NP. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res. 2015 Jan 15;75(2):296-305. doi: 10.1158/0008-5472.CAN-14-2277. Epub 2014 Nov 28. PubMed 25432172 ↗
  • Marshall NA, Galvin KC, Corcoran AM, Boon L, Higgs R, Mills KH. Immunotherapy with PI3K inhibitor and Toll-like receptor agonist induces IFN-gamma+IL-17+ polyfunctional T cells that mediate rejection of murine tumors. Cancer Res. 2012 Feb 1;72(3):581-91. doi: 10.1158/0008-5472.CAN-11-0307. Epub 2011 Dec 9. PubMed 22158905 ↗
  • Muraro E, Comaro E, Talamini R, Turchet E, Miolo G, Scalone S, Militello L, Lombardi D, Spazzapan S, Perin T, Massarut S, Crivellari D, Dolcetti R, Martorelli D. Improved Natural Killer cell activity and retained anti-tumor CD8(+) T cell responses contribute to the induction of a pathological complete response in HER2-positive breast cancer patients undergoing neoadjuvant chemotherapy. J Transl Med. 2015 Jun 27;13:204. doi: 10.1186/s12967-015-0567-0. PubMed 26116238 ↗
  • Shapiro GI, Bell-McGuinn KM, Molina JR, Bendell J, Spicer J, Kwak EL, Pandya SS, Millham R, Borzillo G, Pierce KJ, Han L, Houk BE, Gallo JD, Alsina M, Brana I, Tabernero J. First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95. doi: 10.1158/1078-0432.CCR-14-1306. Epub 2015 Feb 4. PubMed 25652454 ↗
  • Fruman DA, Meyers RE, Cantley LC. Phosphoinositide kinases. Annu Rev Biochem. 1998;67:481-507. doi: 10.1146/annurev.biochem.67.1.481. PubMed 9759495 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 18, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03698383
Lead sponsor
Korean Cancer Study Group
Responsible party
Kyong-Hwa, Park (Professor, Korean Cancer Study Group) — Principal investigator
First posted
Oct 9, 2018
Start date
Dec 3, 2019
Primary completion
Oct 2021 (estimated)
Completion
Dec 2021 (estimated)
Last update
Feb 18, 2021

Study contacts

Kyong Hwa Park, MD, PhD
Contact
khpark@korea.ac.kr
+821047617651
Jung Yoon Choi, MD
Contact
choijy1905@gmail.com
+821072288510
Kyong Hwa Park, MD, PhD
principal investigator · Korean Cancer Study Group

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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