MULTICENTER, OPEN-LABEL EXPANDED ACCESS PROGRAM OF TRASTUZUMAB DERUXTECAN IN SUBJECTS WITH HER2 MUTATED METASTATIC/LOCALLY-ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC)
Trastuzumab deruxtecan for subjects with HER2 mutated metastatic NSCLC
Ueno Shizuko
DAIICHI SANKYO Co.,Ltd.
3-5-1, Nihonbashihonmachi, Chuo-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
Contact for Clinical Trial Information
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
Complete
Mar. 01, 2023
Mar. 17, 2023
30
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
1) Must have provided informed consent for study participation before performance of any study-specific procedure or test.
2) Men or women >= 18 years old.
3) Pathologically documented metastatic/locally advanced NSCLC with a known activating HER2 mutation. The HER2 mutation must be documented from an archival or fresh tumor tissue sample analyzed by laboratory performing testing to Good Laboratory Practice (GLP) standard.
Note: HER2 mutation documented only from a liquid biopsy sample cannot be used for enrollment.
4) Subjects who had previous treatment including platinum therapy in the metastatic/locally advanced setting and not amenable to curative surgery or radiation. The subject must have progressed during or after the last treatment regimen or discontinued because of unacceptable toxicity.
5) Has ECOG PS of 0 to 1.
6) Has left ventricular ejection fraction (LVEF) >= 50% within 28 days before enrollment.
7) Has adequate organ and bone marrow function within 28days before randomization/enrollment. Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 2 weeks prior to randomization. Organ and bone marrow function criteria must also be met when laboratory tests are repeated within 3 days of randomization/enrollment as appropriate. Adequate organ/bone marrow function
8) Has adequate treatment washout period before enrollment
9) Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for females and 4 months for males, after the last dose of study drug.
10) Male subjects must not freeze or donate sperm starting at enrollment and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study.
11) Female subjects must not donate, or retrieve for their own use, ova from the time of enrollment and throughout the study treatment period, and for at least 7 months after the final study drug administration. Female subjects must refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to enrollment in this study.
1) Medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV. Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any MI related symptoms should have a cardiologic consultation before enrollment to rule out MI.
2) Has a corrected QT interval (QTcF) prolongation > 470 msec (females) or >450 msec (males) based on average of triplicate12-lead ECG at screening.
3) Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
4) Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study enrollment.
5) Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated.
6) Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
7) Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
8) Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
9) Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
10) Active primary immunodeficiency, known uncontrolled active HIV infection or active hepatitis B or C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Subjects should be tested for HIV prior to randomization/enrollment if required by local regulations or institutional review board (IRB)/ethics committee (EC).
Subjects with past or resolved hepatitis B virus (HBV) infection are eligible only if they meet all of the following criteria*:
- HBsAg(-) (for > 6 months off anti-viral treatment)
- Anti-HBc(+) (IgG or total Ig)
- HBV DNA undetectable
- Absence of cirrhosis or fibrosis on prior imaging or biopsy
- Absence of HCV co-infection or history of HCV co-infection
- Access to a local Hepatitis B expert during and after the study
Such participants should be closely monitored for HBV reactivation.
*Note to author: Consideration should be given to exclusion of all participants with HBV infection if comparator or combination study treatments are associated with a high risk of HBV infection reactivation and are incompatible with anti-viral medications.
11) Has history of receiving live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention.
12) Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade <= 1 or baseline. Note: Subjects may be enrolled with chronic Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to enrollment and managed with standard of care treatment) which the investigator deems related to previous anticancer therapy, such as:
a.Chemotherapy-induced neuropathy
b.Fatigue
c.Residual toxicities from prior IO treatment: Grade 1 or Grade 2 endocrinopathies which may include:
- Hypothyroidism/ hyperthyroidism
- Type I diabetes
- Hyperglycemia
- Adrenal insufficiency
- Adrenalitis
- Skin hypopigmentation (vitiligo)
13) Is pregnant, breastfeeding, or planning to become pregnant.
14) Otherwise considered inappropriate for the study by the investigator.
15) Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.).
16) Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.
17) Prior complete pneumonectomy.
18) Relapsed from or refractory to prior treatment with any agent, including an antibody drug conjugate (ADC), containing a chemotherapeutic agent targeting topoisomerase I.
19) Had prier history of enrollment or randomization in clinical studies of trastuzumab deruxtecan (regardless of trastuzumab deruxtecan administration)
18age old over
No limit
Both
Non-Small Cell Lung Cancer
Trastuzumab deruxtecan will be administered at 5.4 mg/kg by intravenous infusion every 3 weeks.
N/A
N/A
DAIICHI SANKYO Co.,Ltd.
National Hospital Organization Kyushu Cancer Center Institutional Review Board
