Adagloxad Simolenin/OBI-821 in Combination With TACE Therapy in HCC Patients With GALNT14-rs9679162-non-TT Genotype

NCT ID: NCT03608878

Last Updated: 2021-05-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-26
• Study Completion Date: 2019-12-31

Brief Summary

TACE against HCC is the standard of care for BCLC stage B patients. In this exploratory study, the investigators assess the efficacy of TACE with or without adagloxad simolenin/OBI-821 treatment in GALNT14 "non-TT" HCC population.

Detailed Description

Hepatocellular carcinoma (HCC) is the fifth most common solid cancers worldwide and the third leading cause of cancer-related death. Early stage HCC can be cured by surgical removal or non-surgical ablation procedures, albeit a high recurrence rate up to 75% in 5 years remains an unsolved problem. On the other hand, in patients with unresectable HCC, the "standard therapy" is still under intensive clinical investigations. In patients without portal vein occlusion/thrombosis or extrahepatic metastasis, namely Barcelona Clinical Liver Cancer (BCLC) Stage B, transcatheter arterial chemoembolization (TACE) is believed to be an effective palliative treatment. The beneficial effect of TACE on overall survival has been mild to moderate as reviewed in a previous study. Thus, TACE is generally considered a "palliative" therapy. TACE induces tumor necrosis but at the same time, it also induces angiogenesis owing to the increases of hypoxia-inducible factors and endothelial growth factors to trigger regrowth of tumors.

It has been known that GALNT14 genotype is associated with treatment responses. Patients with GALNT14 "TT" genotype response well to both TACE and chemotherapy.

A new immunotherapy is directed against Globo H, a carbohydrate antigen that is expressed at high levels on the surface of a variety of tumor cells. These Globo H-specific antibodies can effectively induce complement dependent cytotoxicity (CDC) as well as antibody-dependent cell-mediated cytotoxicity (ADCC) by IgM and IgG, respectively, together with other cellular immune responses to kill tumors. In the clinical setting, Globo H has been evaluated as the target of active immunotherapy in a few clinical trials including an ongoing Phase II/III trial of adagloxad simolenin/OBI-821 sponsored by OBI Pharma, Inc., as a potential treatment for stage IV metastatic breast cancers and possibly other cancer types expressing Globo series TACAs. Although vaccination with adagloxad simolenin/OBI-821 did not improve progression-free survival (PFS) in patients with previously treated metastatic breast cancer, in a post-hoc analysis, patients who developed a humoral immune response to Globo H had a longer PFS than those who did not, indicating that adagloxad simolenin/OBI-821 treatment could be of benefit when an antibody response can be developed.

Furthermore, overexpression of tumor-specific antigen Globo H can contribute to enhanced tumor angiogenesis and tumor-associated immune suppression, and in turn, positively correlate with tumor aggressiveness and poor survival in patients. In the present study, only "non-TT" (less favorable) groups will be enrolled and the patients will be randomized to examine the hypothesis that the TACE + adagloxad simolenin/OBI-821 treatment is beneficial in the BCLC class B, advanced HCC patients.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TACE alone arm

TACE (Transarterial Chemoembolization)

Group Type: ACTIVE_COMPARATOR

TACE

Intervention Type: PROCEDURE

Transarterial chemoembolization

adagloxad simolenin arm

TACE plus adagloxad simolenin/OBI-821 adjuvant therapy

Group Type: EXPERIMENTAL

adagloxad simolenin/OBI-821

Intervention Type: BIOLOGICAL

Adagloxad simolenin (OBI-822) is a glyco-conjugated protein comprised of a carbohydrate tumor antigen. Globo H allyl glycoside is covalently linked to a carrier protein KLH, presented in a dominant trimer form with molecular weight between 1200-1395 kDa., to form Adagloxad simolenin (OBI-822) (Globo H-KLH) OBI-821 is a saponin based adjuvant structurally similar to descriptions found in the literature for another adjuvant, QS-21.

Adagloxad simolenin will be mixed with OBI-821 before administration.

TACE

Intervention Type: PROCEDURE

Transarterial chemoembolization

Interventions

adagloxad simolenin/OBI-821

Adagloxad simolenin (OBI-822) is a glyco-conjugated protein comprised of a carbohydrate tumor antigen. Globo H allyl glycoside is covalently linked to a carrier protein KLH, presented in a dominant trimer form with molecular weight between 1200-1395 kDa., to form Adagloxad simolenin (OBI-822) (Globo H-KLH) OBI-821 is a saponin based adjuvant structurally similar to descriptions found in the literature for another adjuvant, QS-21.

Adagloxad simolenin will be mixed with OBI-821 before administration.

Intervention Type: BIOLOGICAL

TACE

Transarterial chemoembolization

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Confirmed Diagnosis of HCC

2. Has a Globo-H or SSEA-3 positive tumor as determined by IHC

3. Never received TACE/ chemotherapy/ radiotherapy or targeted agents prior to this study.

4. Patients should be in BCLC clinical stage B (multinodular asymptomatic tumors without extra-hepatic spread or portal vein invasion) with or without unilateral secondary or tertiary branches of portal vein invasion.

5. Child-Pugh functional class A or B.

6. GALNT14- rs9679162 "non TT" genotype

7. At least 1 measurable lesion must be present.

8. ECOG performance status 0 to 1.

9. Age > 20 years

10. Both men and women enrolled in this trial must use adequate birth control measures during the course of the trial and 4 weeks after last treatment

11. Informed consent must be obtained prior to perform any study procedure.

12. Total bilirubin < 3.0 mg/dL with no evidence of biliary tract obstruction.

13. Appropriate Serum alanine aminotransferase, aspartate aminotransferase, Absolute neutrophil count, Platelets and Serum creatinine

(16) Antiviral treatment for hepatitis B or C is allowed except for interferon.

Exclusion Criteria

1. BCLC stage A.

2. Presence of extrahepatic metastasis or main portal vein thrombosis.

3. Child-Pugh score = C.

4. Significant cardiac disease as determined by investigator.

5. Serious bacterial infection requiring systemic antibiotics.

6. Pregnancy

7. Expected non-compliance.

8. Uncontrolled illness including, but not limited to, ongoing infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness.

9. Bleeding esophageal or gastric varices within three months without ligation or sclerosis injection therapy.

10. Subjects with known HIV infection.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Chau-ting, Yeh

Director, Liver Research Center; Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Chau-Ting Yeh, MD

Role: PRINCIPAL_INVESTIGATOR

LinKou Chang Gung Menorial Hospital

Locations

Linkou Chang Gung Memorial Hospital

Taoyuan, Taoyuan, Taiwan

Countries

Taiwan

Other Identifiers

CGMH/TMUH/VGH-OBI822-HCC001

Identifier Type: -

Identifier Source: org_study_id