Safety, Pharmacokinetics (PK) and Efficacy of AI-061, A 1:1 Co-formulation of AI-025 (Anti-PD-1) and ONC-392 (Anti-CTLA-4) Antibodies in Advanced Solid Tumors: An Open-Label Phase 1 Study

Plain English Summary

Safety, PK and Efficacy of AI-061 in Advanced Solid Tumors is a Phase 1 clinical trial sponsored by OncoC4, Inc. studying Melanoma, Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, High Grade Serous Adenocarcinoma of Ovary, Primary Peritoneal Carcinoma, Fallopian Tube Cancer, Endometrial Cancer, Cervical Cancer, Renal Cell Carcinoma, Bladder Cancer. This trial tests a new combination drug called AI-061, which includes two types of cancer-fighting antibodies (anti-PD-1 and anti-CTLA-4). It is for adults with advanced solid tumors that have spread and did not respond to previous treatments. Participation involves receiving the study drug, with regular check-ups and tests to monitor safety and effectiveness. Alternative treatments may include other types of chemotherapy, immunotherapy, or targeted therapies, depending on the specific cancer type and prior treatments. The trial aims to enroll 18 participants.

Official Summary

AI-061 is a co-formulation drug product (DP) consisting of 1:1 ratio mix of AI-025, an anti-PD-1 antibody, and ONC-392, an anti-CTLA-4 antibody. This is a dose escalation study to identify the maximum toxicity dose (MTD) or the recommended phase 2 dose (RP2D).

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with specific types of advanced solid tumors. Patients must have tumors that can be measured and have not responded to prior treatments. Individuals with good general health and organ function are eligible. Patients with active brain or spinal cord tumors, or certain autoimmune diseases requiring strong medication, cannot participate. This trial is studying Melanoma, Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, High Grade Serous Adenocarcinoma of Ovary, Primary Peritoneal Carcinoma, Fallopian Tube Cancer, Endometrial Cancer, Cervical Cancer, Renal Cell Carcinoma, Bladder Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcomes measure how safe the drug is, what the highest tolerable dose is, and what dose is best for future studies, which helps determine if the drug can be given safely and effectively. The specific primary outcome measures are: Dose Limiting Toxicity (DLT) (21 days after first treatment); Maximum Toxicity Dose (MTD) (21 day after first treatment); Recommended Phase II Dose (RP2D) (21 days after first treatment); Incidence of treatment emergent adverse events (TEAE) (From the day with first treatment to 90 days after the last treatment.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial is important because it explores a novel combination therapy that targets two key pathways in the immune system, potentially offering a new treatment option for patients with advanced cance This research targets Melanoma, Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, High Grade Serous Adenocarcinoma of Ovary, Primary Peritoneal Carcinoma, Fallopian Tube Cancer, Endometrial Cancer, Cervical Cancer, Renal Cell Carcinoma, Bladder Cancer, where improved treatment options are needed.

Investor Insight

This Phase 1 trial of a novel dual-action immunotherapy combination signals a significant investment in exploring new cancer treatment strategies, with potential for broad application across various s Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of AI-061 compared to other available treatments. Understand the schedule of visits, tests, and procedures involved in the trial. Be prepared for regular blood tests and imaging scans to monitor your health and the tumor's response. The trial is being conducted at 5 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 18 participants

Interventions

• DRUG: AI-061 — A 1:1 Co-formulation of AI-025 (Anti-PD-1) and ONC- 392 (Anti-CTLA-4) Antibodies.

Primary Outcomes

• Dose Limiting Toxicity (DLT) (21 days after first treatment)
• Maximum Toxicity Dose (MTD) (21 day after first treatment)
• Recommended Phase II Dose (RP2D) (21 days after first treatment)
• Incidence of treatment emergent adverse events (TEAE) (From the day with first treatment to 90 days after the last treatment.)

Secondary Outcomes

• Cmax of AI-061 (Frequent PK samplings in cycle 1 and cycle 3, pre-dose and post-dose samples in other cycles and End of Treatment. Up to 1 year.)
• The serum half-life of AI-061 (Frequent PK samplings in cycle 1 and cycle 3, pre-dose and post-dose samples in other cycles and End of Treatment. Up to 1 year.)
• Objective Response Rate (ORR) (Up to 1 year.)
• Progression free survival (PFS) (Up to 1 year.)
• Overall survival (OS), (Up to 1 year.)

Full Eligibility Criteria

Inclusion Criteria:

1. Patient is greater or 18 years of age on the day of signing the informed consent.
2. All genders. Female subject with pregnancy potential must have a negative pregnancy test.
3. Patient must have a performance status of less than or equal to 1 on the ECOG Performance Scale.
4. Patients must have a histological or cytological diagnosis of solid tumors and have progressive locally advanced or metastatic disease.
5. Measurable disease as determined by RECIST v1.1 (either tumor lesion or lymph node lesion or both): Tumor mass: Must be accurately measurable in at least 1 dimension (longest diameter to be recorded) with a minimum size of: 10 mm by computed tomography (CT) scan (CT scan slide thickness must be less than 5 mm). Or: 20 mm by chest X-ray (if clearly defined and surrounded by aerated lung).

   Malignant lymph nodes: greater than or equal to 15 mm in short axis when assessed by CT scan (CT scan slice thickness must be \<5 mm). The measurement should be two dimensions at axial plane. The short axis should be in perpendicular to long diameter.
6. Patient must have adequate organ function as indicated by the laboratory values. LDH less than or equal to ULN.
7. Voluntary agreement to participate as evidenced by written informed consent.
8. Female patient: agreement on contraceptive methods.
9. Male patient: agreement on contraceptive methods.
10. Life expectancy greater than or equal to 12 weeks.

Exclusion Criteria:

Patients who have not recovered to NCI CTCAE v5.0 less than or equal toGrade 1 from an adverse event (AE) due to cancer therapeutics except endocrinopathy or the chemotherapy-associated peripheral neuropathy (motor or sensory) that has recovered to CTCAE v5.0 less than or equal to Grade 2 will be allowed. The washout period for cancer therapeutic drugs should be 21 days prior to the first AI-061 dose for chemotherapy, radiation, or targeted therapy or 28 days prior to the first AI-061 administration for monoclonal antibody therapy. Best supportive care, such as thyroxine, insulin, steroid replacement treatment, blood transfusion, and therapy for non-cancer conditions are allowed.

2\. Patients who are currently enrolled in any other clinical trial testing an investigational agent or device, or with concurrent other systemic cancer therapeutics.

3\. Patients who are on chronic systemic steroid therapy at doses higher than 10 mg/day prednisone or equivalent within 7 days before the first treatment.

4\. Patients who have active brain metastases or leptomeningeal metastases. 5. Patients who have an active infection requiring systemic IV antibiotics within 14 days prior to administration of AI-061. Regular treatment of urinary tract infection (UTI) and/or topical treatment are allowed.

6\. Patients who, in the opinion of the treating Investigator, have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or make study participation not in the best interest of the patient. The investigator should discuss this with the Sponsor.

7\. Patients with known psychiatric or substance abuse disorders that in the opinion of the investigator, would interfere with cooperation with the requirements of the trial.

8\. Patients who are pregnant or breastfeeding.

9\. Patients with active autoimmune diseases that require immunosuppressant treatment other than 10 mg per day or lower prednisone. Patients with inflammatory bowel disease or myasthenia gravis will be excluded.

Trial Locations

• St. Vincent's Private Hospital, Darlinghurst, New South Wales, Australia
• Mater Misericordiae Ltd., Brisbane, Queensland, Australia
• Tasman Oncology Research, Southport, Queensland, Australia
• Cancer Research SA, Adelaide, South Australia, Australia
• Southern Oncology Clinical Research Unit, Bedford Park, South Australia, Australia

Frequently Asked Questions

Related Conditions

• Melanoma
• Non-Small Cell Lung Cancer
• Head and Neck Squamous Cell Carcinoma
• Ovarian Cancer (High Grade Serous Adenocarcinoma)
• Primary Peritoneal Carcinoma
• Fallopian Tube Cancer
• Endometrial Cancer
• Cervical Cancer
• Renal Cell Carcinoma (Kidney Cancer)
• Bladder Cancer

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