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

NCT05930951 | Terminated Phase 1 DMC

• 1 other identifier: 2023-503270-20-00
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Adenoid Cystic Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

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

  through study completion, an average of 1 year"

Study Arms (2)

OBT076 only

ACTIVE COMPARATOR

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.

Drug: OBT076

OBT076 -Balstilimab

EXPERIMENTAL

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.

Drug: OBT076; Drug: Balstilimab

Interventions

OBT076 DRUG

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; OBT076 only

Balstilimab DRUG

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

OBT076 -Balstilimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female ≥ 18 years
• ECOG PS 0-1
• Histologically confirmed Adenoid Cystic Carcinoma (AdCC) of the Head and Neck or trachea
• Histologically and/or radiologicaly documented recurrent or metastatic AdCC not amenable to surgery and/or radiotherapy
• Patients with confirmed disease progression at study entry. The screening radiological evaluation (CT/MRI of H\&N, chest, pelvis and brain if known or suspected cerebral involvement) should demonstrate disease progression according to RECIST 1.1 when compared to a prior disease assessment done within 6 months period prior to screening
• Measurable disease by CT scan or MRI according to RECIST 1.1 criteria
• Adequate haematologic, renal and hepatic function as indicated by (using CTCAE v5.0):
• Absolute neutrophil count ≥ 2.0 × 109/L
• Platelets ≥ 100 × 109/L
• Hemoglobin ≥ 9.0 g/dL (blood transfusions during Screening are not permitted)
• White blood cells ≥ 2 000/mm3
• AST and ALT ≤ 2.5 × ULN in the absence of liver metastases or \< 5 × ULN in the presence of liver metastases
• Serum creatinine \< 1.5 × ULN
• Total bilirubin ≤ 1.5 × ULN (except Gilbert Syndrome \< 3.0 mg/dL)
• Potassium within normal range according to local lab, or correctable with supplements

You may not qualify if:

• Pretreatment with a programmed cell death protein (PD-1), PD-L1 or cytotoxic T- lymphocyte antigen 4 (CTLA-4) therapy or any other immuno-checkpoint inhibitors.
• Prior chemotherapy within 28 days before study drug administration.
• Prior systemic anticancer therapy (regardless if approved or investigational therapy) within 5 halflives of study drug administration
• Major surgery within 14 days before study drug administration
• Patients have not recovered from the toxicities (CTCAE v5.0 grade \> 1) of prior anticancer therapy
• Prior curative radiotherapy ≤ 4 weeks or palliative radiotherapy ≤ 2 weeks before study drug administration, and/or from whom ≥ 30% of the bone marrow was irradiated
• Patients with brain metastasis, except if treated with curative stereotactic radiotherapy
• History of another malignancy within the last 2 years prior to randomization, with the exception of completely resected non-melanoma cell skin cancer outside the head and neck area or completely resected stage I breast cancer, gleason 6 localised prostate cancer, or completely resected in-situ non-muscular invasive bladder, cervix and/or uterine carcinomas.
• Documented or suspected hypersensitivity or other contraindication to study drug or any excipients used in the manufacture of OBT076 or Balstilimab
• Active or chronic corneal disorder or Sjogren's syndrome
• Known history of infection with human immunodeficiency virus (HIV). If unknown history of HIV, an HIV screening test is to be performed and participants with positive serology for HIV-1/2 must be excluded.
• Known chronically active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Known active Covid 19 infection.
• Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 28 days prior to study drug administration. The use of the inactivated seasonal influenza vaccine (Fluzone®) and covid vaccine is allowed.
• Active or prior history of disease/medical condition listed below:

Sponsors & Collaborators

• Groupe Oncologie Radiotherapie Tete et Cou: lead

Study Sites (1)

Hôpital Saint-André (Chu de Bordeaux)

Bordeaux, 33075, France

Location

MeSH Terms

Interventions

balstilimab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2023
• First Posted: July 5, 2023
• Study Start: November 29, 2023
• Primary Completion: October 9, 2024
• Study Completion: October 9, 2024
• Last Updated: May 9, 2025

Record last verified: 2025-05

Locations

FR (1)