A Phase I/II.a Investigator-initiated Study of ADR-001 in Combination With Nivolumab in Cancer Patients With Acquired Resistance to Immune Checkpoint Inhibitors

JRCT ID: jRCT2033240023

Registered date:10/04/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Solid cancers such as lung cancer, esophageal cancer, stomach cancer, etc.
• Date of first enrollment: 24/04/2024
• Target sample size: 20
• Study type: Interventional
• Intervention(s): Intramuscular injection of the investigational drugs and intravenous infusion of the concomitant drugs.

Outcome(s)

Primary Outcome

- Tolerability and Safety
- Efficacy (number of subjects rated SD or better based on the Response Evaluation Criteria for Solid Tumors (RECIST ver 1.1) guidelines at Day 85)

Secondary Outcome

- Clinical laboratory tests for safety evaluation, ECOG PS, ECG and vital signs, etc.
- Disease control rate (DCR: Percentage of subjects with SD, PR, or CR) based on the Response Evaluation Criteria for Solid Tumors (RECIST ver 1.1) guidelines at Day 85: investigator's assessment.
- Objective response rate (ORR: percentage of subjects with PR or CR) based on RECIST ver 1.1 guidelines at Day 85: investigator's assessment.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Japanese patients aged 20 years or older at the time of consent.
2. patients diagnosed with solid tumors such as non-small cell lung cancer, esophageal cancer, gastric cancer, etc. by histopathological examination, previously treated with an immune checkpoint inhibitor, and who have achieved a best response of stable disease (SD) or better by the efficacy evaluation using RECIST, and who have been in SD for at least 6 months, or after PR or CR, Progressive disease (PD) is confirmed after PR or CR.
3. Patients on or after the second-line treatment.
4. Patients with an ECOG PS of 0 or 1 within 28 days prior to the start of the investigational product or drug.
5. Patients expected to be alive for at least 3 months at the time of consent.
6. Patients who can be hospitalized at the time of the first dose.
7. Patients with at least one measurable lesion on RECIST version 1.1.
8. Patients who have not received chemotherapy, immunotherapy (tumor vaccine, cytokine, etc.), or surgery within 4 weeks prior to the administration of the investigational product or drug.
9. Patients who have not received more than 50 Gy of radiation therapy within 4 weeks prior to the administration of the investigational product or drug. Patients who have not received radiopharmaceuticals (e.g., strontium) within 8 weeks prior to the administration of the investigational product or drug.
10. Women of childbearing potential who have agreed to use contraception from the time of consent for at least one year after the last dose of the investigational product or drug.
11. For males, patients who have agreed to use contraception from the time of initiation of treatment with the investigational product and study drug for at least one year after the last dose of the investigational product and study drug.
12. Patients who meet the following criteria for laboratory tests performed within 28 days prior to administration of the investigational product or drug.
-White blood cell count > 2000/mm3 and neutrophil count > 1500/mm3
-Platelet count greater than or equal to 75,000/mm3
-Hemoglobin greater than or equal to 9.0 g/dL
-AST (GOT) less than 75 U/L*
-ALT (GPT) less than 105 U/L*
-Total bilirubin less than 1.5 mg/dL
-Creatinine less than 1.5 mg/dL
-SpO2 greater than 90%
*: In patients with confirmed liver metastases, AST and ALT must be less than 5 times the upper limit of the institutional reference value.

Exclude criteria

1. Patients with a history of severe drug hypersensitivity.
2. Patients with multiple cancers. However, patients with epithelial and intramucosal carcinoma lesions may be enrolled.
3. Patients with symptomatic central nervous system metastases, including symptomatic brain metastases.
4. Patients with a history of or complications of interstitial pneumonia or pulmonary fibrosis.
5. Patients with a history of organ transplantation.
6. patients with residual adverse effects of previous treatment or surgical therapy that may affect the safety evaluation of the investigational product or drug.
7. patients with concomitant autoimmune diseases or a history of chronic or recurrent autoimmune diseases or diseases requiring systemic steroids or immunosuppressive agents (e.g., patients with diseases for which systemic use of immunosuppressive agents or corticosteroids cannot be discontinued 4 weeks prior to administration of the investigational product or drug) (e.g., patients with diseases that do not allow systemic use of immunosuppressive drugs or corticosteroids to be discontinued 4 weeks prior to administration of study product or study drug). However, patients who are experiencing immune-related adverse reactions (irAEs) that can be controlled with appropriate treatment are considered eligible.
8. Patients whose bone pain associated with bone metastases has not stabilized with narcotic analgesics at the same dosage and administration.
9. Patients with positive HBs antigen and HCV antibody tests.
10. Patients with known HIV positivity.
11. Pregnant, lactating, or possibly pregnant patients (lactating patients are not allowed to participate in this study even if they discontinue breastfeeding).
12. Patients who have participated in another clinical trial within 4 weeks prior to administration of the investigational product or drug.
13. Patients who have been administered ADR-001 in the past.
14. Other patients who are judged by the investigator to be unsuitable for the clinical trial.

Related Information

• Primary Sponsor: Wada Satoshi