Overview

A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients With HER2 Positive Advanced Gastric Cancer

Status:
Active, not recruiting
Trial end date:
2022-02-01
Target enrollment:
0
Participant gender:
All
Summary
The Phase 1b study is an open-label, multicenter dose escalation study designed to assess the safety, tolerability, immunogenicity and recommended phase 2 dose (RP2D) of IMU-131. The RP2D will be evaluated in the dose expansion Phase 2 study. The Phase 2 study is a randomized, open label comparison of IMU-131 plus standard of care chemotherapy versus standard of care chemotherapy alone.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Imugene Limited
Treatments:
Capecitabine
Cisplatin
Fluorouracil
Oxaliplatin
Criteria
Inclusion Criteria:

1. Patient has been informed of the investigational nature of this study and has given
written informed consent in accordance with institutional, local, and national
guidelines;

2. Age ≥ 20 years old;

3. Life expectancy of at least 12 weeks;

4. Phase 1b: No prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer
within 6 months prior to Day 0; Phase 2: No prior chemotherapy or radiotherapy for
advanced gastric or GEJ cancer within 3 months prior to Day 0;

5. Metastatic gastric or GEJ adenocarcinoma, or locally advanced disease not amenable to
surgical resection;

6. HER2/neu overexpression (3+ by immunohistochemistry (IHC) or if IHC 2+ confirmed by
fluorescent in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]).
Patients with IHC 2+ expression without confirmation of overexpression by fluorescent
in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]) may be
included in Phase 1b with agreement of Imugene Limited;

7. Phase 1b: ECOG performance status 0-1; Phase 2: ECOG performance status 0-2;

8. At least one measurable lesion as defined by RECIST 1.1 criteria. Patients with
non-measurable lesions may be included in Phase1b with agreement of Imugene Limited;

9. Adequate left ventricular ejection function at baseline, defined as LVEF > 50% by
echocardiogram or MUGA scan (Multi Gated Acquisition Scan);

10. Adequate hematologic function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet
count ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL;

11. Adequate liver function evidenced by bilirubin ≤ 1.5 x laboratory upper limit of
normal [ULN], and ALT and AST ≤ 3 x laboratory ULN if no liver involvement or ALT and
AST ≤ 5 times laboratory ULN with liver involvement;

12. Adequate renal function (creatinine ≤ 1.5 x laboratory ULN);

13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures.

14. Male and female patients of childbearing potential must agree to use a highly
effective method of contraception throughout the study and for at least 28 days after
the last dose of assigned treatment (see section 4.3 for details). A patient is of
childbearing potential if, in the opinion of the investigator, he/she is biologically
capable of having children and is sexually active.

Exclusion Criteria:

1. Previous treatment with trastuzumab or any other HER2/neu targeting antibody or agent;

2. Continuous systemic treatment with either corticosteroids (>10 mg daily prednisone
equivalents) or other immunosuppressive medications within 4 weeks prior to first dose
of study treatment. Inhaled or topical steroids and physiological replacement doses of
up to 10 mg daily prednisone equivalents are permitted in the absence of active
auto-immune disease;

3. Prior organ transplant;

4. Phase 1b: Patient not considered a candidate for 5-FU, capecitabine, or cisplatin
chemotherapy; Phase 2: Patient not considered a candidate for 5-FU, capecitabine,
cisplatin or oxaliplatin chemotherapy;

5. History of documented congestive heart failure; angina pectoris requiring antianginal
medication; evidence of transmural infarction on ECG; poorly controlled hypertension;
clinically significant valvular heart disease; high risk uncontrolled arrhythmias; or
New York Heart Association (NYHA) class II heart disease;

6. If on warfarin (Coumadin®) or other vitamin K antagonists;

7. Concurrent active malignancy except for adequately controlled limited basal cell
carcinoma of the skin;

8. Peripheral neuropathy or hearing loss of NCI CTCAE Grade > 2;

9. History of uncontrolled seizures, central nervous disorders or psychiatric disability
judged by the investigator to be clinically significant and precluding informed
consent, participation in the study, or adversely affecting compliance to study drugs;

10. Active infection requiring IV antibiotics;

11. Positive for human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active
hepatitis B (HBsAg reactive) or active hepatitis C (HCV ribonucleic acid [RNA]
qualitative) infection;

12. Pregnant or lactating females;

13. Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic
biopsy) within 1 week prior to study entry;

14. Has received a live-virus vaccination within 4 weeks of first study vaccination.
Seasonal flu vaccines that do not contain live virus are permitted;

15. Current or recent (within 4 weeks of first IMU-131 vaccination) treatment with another
investigational drug or participation in another investigational study.

16. Phase 2: Patients with a known diphtheria toxoid hypersensitivity.