Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Carcinoma

Carcinoma, Adenoid Cystic

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Adenoid Cystic Carcinoma

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulins, Intravenous

OBT076, administration at 3mg/kg, (IV ≥ 3h infusion) on Day 1 every 21 days (3-week cycle) until disease progression, unacceptable toxicity, intercurrent conditions that preclude continuation of treatment or patient refusal whichever comes first.

3 cycles of OBT076, administration at 3mg/kg, IV (≥ 3h infusion) on Day 1 every 21 days (3-week cycle) followed by Balstilimab, administration at 450mg, IV, on Day 1 every 21 days (3-week cycle) until disease progression, unacceptable toxicity, intercurrent conditions that preclude continuation of treatment or patient refusal whichever comes first.

OBT076 is an ADC constituted by a fully human immunoglobulin 1 (IgG1) antibody directed against the CD205/Ly75 antigen (MBH1309), inducing potent cytotoxic and anti-tumor activity

OBT076

Balstilimab is a human monoclonal antibody that targets programmed cell death protein 1 (PD-1).

Balstilimab

JEAN BOURHIS, Pr

Frédéric ROLLAND, Dr

AMAURY DASTE

Adenoid cystic carcinoma (AdCC) is a rare salivary gland malignant tumor that accounts for approximately 1-3% of all head and neck cancers. AdCC is often charaterised by a long natural history with a propensity for indolent but relentless growth and dissemination. Local recurrences and late distant metastases are common findings in about 35% of the patients and associated with a poor prognosis1. AdCC is among the most lethal salivary gland tumors2 with no proven therapy for metastatic disease. Little is known about endogenous immune response directed against AdCC. However, in a relatively large series of 28 AdCC tumor, the immune profiling has shown in most tumors high and frequent programmed death ligand 2 (PD-L2) expression and PD-L1 was generally not expressed on tumor and infiltrating cells3.

The Antibody Drug Conjugates (ADCs) are emerging as a novel therapeutic option in cancer treatment that looks promising for solid tumors. An experimental CD205/Ly75-directed ADC, OBT076 induce potent cytotoxic and antitumor activity. Recently, the combination of immunohistochemistry (IHC) and tissue micro array (TMA) was performed in a series of 46 AdCC, showing a unique profile with both frequent and high expression of CD205/Ly75, much higher than for other solid tumors. In a phase I study, OBT076 demonstrated promising results for 3 patients with 2 partial responses and 1 complete response for a gastric cancer4. In this last patient, analysis showed an increase in PD1+, CD4+ and CD8+ cells suggesting that OBT076 activates the patient's immune response against the tumor, especially PD-1 targeted therapies4.

Based on this rational and on the high level of expression of CD205/Ly75 in AdCC, the hypothesis tested in this study is that OBT076 could be a potential effective treatment for R/M AdCC, which is an orphan lethal disease. The efficacy of OBT076 will be tested either alone or followed by an anti PD-1 inhibitor (Balstilimab) with the hypothesis that OBT076 will induce immune infiltrate that could restore sentivity to PD-1 targeting.

Study of OBT076 Associated or Not in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck

A Phase Ib Study of OBT076 or OBT076 Followed by Balstilimab in Patients With Recurrent or Metastatic (R/M) Adenoid Cystic Carcinoma (AdCC) of the Head and Neck (H&N)

ORR based on the best tumor response evaluated by investigator assessment using RECIST 1.1 criteria will be the primary endpoint

Groupe Oncologie Radiotherapie Tete et Cou

Head and Neck Neoplasms

Antineoplastic Agents

Amino Acids

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Imatinib

Sandrine Faivre, MD

Caroline Robert, MD

This is a Phase II study of imatinib (Glivec) administered as a daily oral treatment in patients with recurrent/metastatic adenoid cystic carcinoma of the head and neck overexpressing KIT.

Patients with relapsing and/or metastatic adenoid cystic carcinoma of the salivary gland of the head and neck are usually poor responders to conventional cytotoxic chemotherapy.

The investigation of proliferation pathways involving tyrosine kinase receptors such as c-kit receptor (KIT) and PDGF receptor may allow to identify a molecular target for novel therapeutic approaches in patients with adenoid cystic carcinoma who failed locoregional treatment.

Several publications in the literature and the pathological study we conducted in Institut Gustave Roussy show that KIT overexpression is observed in at least 80-90% of the cases of adenoid cystic carcinoma, supporting the investigation of imatinib in patients with adenoid cystic carcinoma overexpressing KIT.

Imatinib is an orally administrated, well tolerated compound that could be given on an outpatient schedule to patients with relapsing/metastatic adenoid cystic carcinoma of the head and neck.

Because of the infrequent occurrence of salivary gland malignancies, a multicenter trial will be mandatory and the study will include at least 2 centers represented by Institut Gustave Roussy, Villejuif; and Hôpital Georges-Pompidou, Paris.

Study of Imatinib (Glivec) in Patients With Adenoid Cystic Carcinoma of the Head and Neck

Phase II Study of Imatinib (Glivec) Administered as a Daily Oral Treatment in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma of the Head and Neck Overexpressing KIT

Gustave Roussy, Cancer Campus, Grand Paris

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of OBT076 Associated or Not in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck	NCT05930951	Adenoid Cystic ...	OBT076 Balstilimab	18 Years -	Groupe Oncologie Radiotherapie Tete et Cou
Study of Imatinib (Glivec) in Patients With Adenoid Cystic Carcinoma of the Head and Neck	NCT00180921	Cancer of the H... Carcinoma, Aden...	Imatinib	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris

Spots Global Cancer Trial Database for adenoid cystic carcinoma of the head and neck