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Non-small Cell Lung CancerPhase 1/2NCT05016544

Inetetamab in Combination With Pyrotinib in HER2 Mutant or Amplified Advanced Non-small Cell Lung Cancer

A Phase 1/2 study testing inetetamab and Pytotinib in people with Non-small Cell Lung Cancer, run by Sun Yat-sen University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a Phase 1, open-label study to evaluate the safety and the efficacy of inetetamab in combination with pyrotinib in patients in HER2 mutant or amplified patients with advanced non-small cell lung cancer Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
inetetamab and Pytotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteChina
Study dates
28 Jul 2021to 1 Feb 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age over 18;
  • Histologically or cytologically documented metastatic NSCLC, HER2 activation amplification or mutation stage IIIB-IV NSCLC patient;
  • At least 1 measurable lesion according to RECIST 1.1;
  • ECOG score 0 or 1;
  • Life expectancy of at least 3 months;
  • Within one week before admission, blood routine examination was basically normal:
Show all 16Show fewer
  • hemoglobin ≥90g/L or ≥5.6mmol/L;
  • neutrophil count (ANC) ≥ 1.5 × 10 ^ 9 / L;
  • platelet count (PLT) ≥ 100 × 10 ^ 9 / L;
  • Liver and kidney function tests were basically normal within one week before enrollment;
  • total bilirubin (TBIL) ≤ 1.5 × upper limit of normal value (ULN);
  • alanine aminotransferase (ALT / AST) ≤ 2.5 × ULN (liver metastasis patients ≤ 5xuln);
  • serum creatinine ≤ 1.5 × ULN;
  • Partially activated thrombin time(APTT)≤ 1.5 × ULN;
  • For fertile women had negative blood pregnancy tests 7 days before screening;
  • willing to participate and sign the informed consent in person.

Who cannot join

  • Patients who have received anti-HER2 monoclonal antibody therapy;
  • Have received chemotherapy, biotherapy, targeted therapy, immunotherapy and other anti-tumor therapies within 4 weeks prior to the first use of the study drug including: oral small molecule targeted drugs within 2 weeks prior to the first use of the study drug or within 5 half-lives of known drugs (depending on the time);Radiotherapy was performed within 2 weeks prior to the first administration of the study drug;
  • Have received other clinical study drugs within 4 weeks prior to the first study drug administration;
  • Patients who underwent major surgery within 4 weeks prior to the first dosing of the study drug(except needle biopsy or significant trauma);
  • Those who have been known to have allergic history to the drug components of this regimen;
  • Study drugs that had used a CYP3A4 inhibitor, inducer, or a narrow therapeutic window with a CYP3A4-sensitive substrate ,P-ep strong inducer and inhibitor within 14 days before first administration;
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  • The adverse reactions of previous antitumor therapy have not recovered to CTCAE 5.0 grade 1(Hair loss and other toxicities were excluded for which the researchers judged no safety risk);
  • Patients with central nervous system metastasis and clinical symptoms;
  • History of immunodeficiency, including positive HIV test, or suffering from other acquired, congenital immunodeficiency diseases, or history of organ transplantation;
  • Active hepatitis B (HBV virus titer 1000 copies /ml or 200IU/ml);Hepatitis C virus, syphilis infection;
  • Severe heart disease or discomfort, including, but not limited to, the following: complete left bundle branch block or degree atrioventricular block, history of myocardial infarction, angioplasty, coronary artery bridging, patients with prolonged QT/QTc interval at baseline (QTcF men >450 ms, women >480ms), significant ventricular arrhythmias (such as ventricular tachycardia), history of heart failure or systolic dysfunction (LVEF < 50%), cardiac failure, New York College of Cardiology (NYHA) grade II or higher, uncontrolled hypertension (systolic blood pressure > 180 mmHg ), history or current history of cardiomyopathy that the investigator judged to have an impact on the study;
  • Inability to swallow medications orally, or that the investigator determines severely affect gastrointestinal absorption;
  • Other malignant tumors in the past 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell carcinoma or in situ cervical cancer and/or breast cancer;
  • Any history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid treatment, or evidence of clinically active interstitial lung disease;
  • Patients with a history of other serious systemic diseases who were judged by the investigator to be unsuitable for clinical trials;
  • Alcohol or drug dependence;
  • Have a clear history of neurological or mental disorders, including epilepsy or dementia;
  • Pregnant and/or breastfeeding;
  • Any other reason the investigator considers the patient is not suitable to participate in the study.

Trial locations and contacts

1 site in 1 country.

Li Zhang, MD. contact

86-20-87343458

zhangli6@mail.sysu.edu.cn

Wenfeng Fang, MD, PhD. contact

86-020-8734-3894

fangwf@sysucc.org.cn

China1 site, 1 recruiting

  • Sun Yat-Sen University Cancer Center

    Guangzhou, Guangdong, 510060

    Li Zhang, professor, 86-20-8734-3458, zhangli6@mail.sysu.edu.cn

    Recruiting

Other trials in China

About this study

Official title: A Phase Ib Clinical Study Evaluating the Safety and Efficacy of Inetetamab in Combination With Pyrotinib in HER2 Mutant or Amplified Patients With Advanced Non-small Cell Lung Cancer

This is a Phase 1, open-label study to evaluate the safety and the efficacy of inetetamab in combination with pyrotinib in patients in HER2 mutant or amplified patients with advanced non-small cell lung cancer

Read the detailed description

This study is a multi-center, opening, dose-escalating phase Ib clinical trial. The aim of the study is to evaluate the safety and efficacy of inetetamab combined with pyrotinib in the treatment of patients in HER2 mutant or amplified patients with advanced non-small cell lung cancer .Primary endpoint of the study is dose-limiting toxicity dosage and safety. Efficacy indicators including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) are as Secondary endpoint. Up to 48 NSCLC patients will be enrolled the treatment will be performed 3+3 dose-escalation phase I design and expanded to phase II study. A treatment cycle lasts 3 weeks,and the combined medication will be continued until the occurrence of toxicity intolerance,disease progression,or death,or patients refuse to continue participating in this clinical study,or the investigators determine that the medication must be terminated.

The recommended initial consistent dose of inetetamab in groups 1-3 are 8 mg/kg, intravenous infusion for more than 90 minutes, and the maintenance dose is 6 mg/kg.

The oral doses of pyrotinib in groups 1-3 were 240 mg, 320 mg, or 400 mg, respectively.

Safety evaluation will be taken according to hematological toxicity, non-hematological toxicity and National Cancer Institute (NCI)-Common Terminology Criteria (CTC) For Adverse Events (AE) V5.0.

Being tested
inetetamab, Pytotinib
Keywords
Non-small Cell Lung Cancer, Inetetamab, Pyrotinib, HER2-activated mutation, HER2-amplification
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • inetetamabDrug

    All dose levels will receive 8 mg/kg loading dose for cycle 1, followed by 6 mg/kg in subsequent cycles, every 3 weeks.

  • PytotinibDrug

    Starting pytotinib Dose of 240mg:

    Cohort 1: pyrotinib 240mg p.o. d1 to d21, q3w; Cohort 2: pyrotinib 320mg p.o. d1 to d21, q3w; Cohort 3: pyrotinib 400mg p.o. d1 to d21, q3w.

Study groups in NCT05016544
Study groupRoleWhat they receive
Inetetamab+PyrotinibExperimentalDose Escalation and Dose Expansion: Inetetamab in combination with Pyrotinib in HER2 mutant or amplified participants with advanced or metastatic NSCLC
Receives: Drug: inetetamab; Drug: Pytotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose escalation

    Number of Participants with a Dose-Limiting Toxicity (DLT)

    Measured: Up to 21 days after the first dose

  2. Incidence of adverse events

    Incidence, severity, and serious adverse events (SAEs) based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

    Measured: Up to 30 days after the last dose of inetetamab or pyrotinib

Secondary outcomes (5)

  1. Objective response rate

    Per RECIST v1.1 criteria, the proportion of patients whose best remission was CR or PR accounted for the total number of evaluable patients.

    Measured: up to12 months

  2. Disease Control Rate

    Per RECIST v1.1 criteria, the proportion of patients whose best remission was CR , PR and SD accounted for the total number of evaluable patients.

    Measured: up to12 months

  3. Progression free survival

    PFS is defined as the time from the date of first dosing till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).

    Measured: 24 months

  4. Overall survival

    Overall survival (OS) is defined as the time from the date of first dosing till death due to any cause.

    Measured: 36 months

  5. Investigation on molecular markers associated with the clinical efficacy and the mechanism of drug resistance

    Using next generation sequencing (NGS) method to detect 22 genes from circulating free DNA (cf-DNA) in patients, periphereal blood sample were collected at baseline, first time tumor efficacy evaluation, and withdrawn study due to disease progression.

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2021
  2. Study start28 Jul 2021
  3. Primary completion1 Aug 2023 (estimated)
  4. Study completion1 Feb 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Sequential assignment by traditional 3+3 dose escalation
Masking
None (open label)
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05016544
Sponsor's protocol ID
2021-FXY-191
Status last verified
Aug 2021
First submitted
8 Aug 2021
Last updated
23 Aug 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cocco E, Lopez S, Santin AD, Scaltriti M. Prevalence and role of HER2 mutations in cancer. Pharmacol Ther. 2019 Jul;199:188-196. doi: 10.1016/j.pharmthera.2019.03.010. Epub 2019 Apr 2.

    PubMed 30951733

  • Pisters KM, Le Chevalier T. Adjuvant chemotherapy in completely resected non-small-cell lung cancer. J Clin Oncol. 2005 May 10;23(14):3270-8. doi: 10.1200/JCO.2005.11.478.

    PubMed 15886314

  • Bonomi PD. Implications of key trials in advanced nonsmall cell lung cancer. Cancer. 2010 Mar 1;116(5):1155-64. doi: 10.1002/cncr.24815.

    PubMed 20087963

  • Stephens P, Hunter C, Bignell G, Edkins S, Davies H, Teague J, Stevens C, O'Meara S, Smith R, Parker A, Barthorpe A, Blow M, Brackenbury L, Butler A, Clarke O, Cole J, Dicks E, Dike A, Drozd A, Edwards K, Forbes S, Foster R, Gray K, Greenman C, Halliday K, Hills K, Kosmidou V, Lugg R, Menzies A, Perry J, Petty R, Raine K, Ratford L, Shepherd R, Small A, Stephens Y, Tofts C, Varian J, West S, Widaa S, Yates A, Brasseur F, Cooper CS, Flanagan AM, Knowles M, Leung SY, Louis DN, Looijenga LH, Malkowicz B, Pierotti MA, Teh B, Chenevix-Trench G, Weber BL, Yuen ST, Harris G, Goldstraw P, Nicholson AG, Futreal PA, Wooster R, Stratton MR. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature. 2004 Sep 30;431(7008):525-6. doi: 10.1038/431525b.

    PubMed 15457249

  • Arcila ME, Chaft JE, Nafa K, Roy-Chowdhuri S, Lau C, Zaidinski M, Paik PK, Zakowski MF, Kris MG, Ladanyi M. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res. 2012 Sep 15;18(18):4910-8. doi: 10.1158/1078-0432.CCR-12-0912. Epub 2012 Jul 3.

    PubMed 22761469

  • Gatzemeier U, Groth G, Butts C, Van Zandwijk N, Shepherd F, Ardizzoni A, Barton C, Ghahramani P, Hirsh V. Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer. Ann Oncol. 2004 Jan;15(1):19-27. doi: 10.1093/annonc/mdh031.

    PubMed 14679114

  • Lara PN Jr, Laptalo L, Longmate J, Lau DH, Gandour-Edwards R, Gumerlock PH, Doroshow JH, Gandara DR; California Cancer Consortium. Trastuzumab plus docetaxel in HER2/neu-positive non-small-cell lung cancer: a California Cancer Consortium screening and phase II trial. Clin Lung Cancer. 2004 Jan;5(4):231-6. doi: 10.3816/clc.2004.n.004.

    PubMed 14967075

  • Perera SA, Li D, Shimamura T, Raso MG, Ji H, Chen L, Borgman CL, Zaghlul S, Brandstetter KA, Kubo S, Takahashi M, Chirieac LR, Padera RF, Bronson RT, Shapiro GI, Greulich H, Meyerson M, Guertler U, Chesa PG, Solca F, Wistuba II, Wong KK. HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy. Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):474-9. doi: 10.1073/pnas.0808930106. Epub 2009 Jan 2.

    PubMed 19122144

  • Shimamura T, Ji H, Minami Y, Thomas RK, Lowell AM, Shah K, Greulich H, Glatt KA, Meyerson M, Shapiro GI, Wong KK. Non-small-cell lung cancer and Ba/F3 transformed cells harboring the ERBB2 G776insV_G/C mutation are sensitive to the dual-specific epidermal growth factor receptor and ERBB2 inhibitor HKI-272. Cancer Res. 2006 Jul 1;66(13):6487-91. doi: 10.1158/0008-5472.CAN-06-0971.

    PubMed 16818618

  • Kris MG, Camidge DR, Giaccone G, Hida T, Li BT, O'Connell J, Taylor I, Zhang H, Arcila ME, Goldberg Z, Janne PA. Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors. Ann Oncol. 2015 Jul;26(7):1421-7. doi: 10.1093/annonc/mdv186. Epub 2015 Apr 21.

    PubMed 25899785

  • Mazieres J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, Besse B, Blons H, Mansuet-Lupo A, Urban T, Moro-Sibilot D, Dansin E, Chouaid C, Wislez M, Diebold J, Felip E, Rouquette I, Milia JD, Gautschi O. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol. 2013 Jun 1;31(16):1997-2003. doi: 10.1200/JCO.2012.45.6095. Epub 2013 Apr 22.

    PubMed 23610105

  • De Greve J, Teugels E, Geers C, Decoster L, Galdermans D, De Mey J, Everaert H, Umelo I, In't Veld P, Schallier D. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer. 2012 Apr;76(1):123-7. doi: 10.1016/j.lungcan.2012.01.008. Epub 2012 Feb 10.

    PubMed 22325357

  • Diaz R, Nguewa PA, Parrondo R, Perez-Stable C, Manrique I, Redrado M, Catena R, Collantes M, Penuelas I, Diaz-Gonzalez JA, Calvo A. Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model. BMC Cancer. 2010 May 11;10:188. doi: 10.1186/1471-2407-10-188.

    PubMed 20459769

  • Wang Y, Jiang T, Qin Z, Jiang J, Wang Q, Yang S, Rivard C, Gao G, Ng TL, Tu MM, Yu H, Ji H, Zhou C, Ren S, Zhang J, Bunn P, Doebele RC, Camidge DR, Hirsch FR. HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib. Ann Oncol. 2019 Mar 1;30(3):447-455. doi: 10.1093/annonc/mdy542.

    PubMed 30596880

  • Zhou C, Li X, Wang Q, Gao G, Zhang Y, Chen J, Shu Y, Hu Y, Fan Y, Fang J, Chen G, Zhao J, He J, Wu F, Zou J, Zhu X, Lin X. Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study. J Clin Oncol. 2020 Aug 20;38(24):2753-2761. doi: 10.1200/JCO.20.00297. Epub 2020 Jul 2.

    PubMed 32614698

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing inetetamab and Pytotinib in people with Non-small Cell Lung Cancer, run by Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 23 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Li Zhang, MD. (86-20-87343458, zhangli6@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose escalation (time frame: Up to 21 days after the first dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05016544, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2021.

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