A Study to Evaluate the Safety and Pharmacokinetics of OC-001 in Patients With Locally Advanced or Metastatic Cancers

Study Overview
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Brief Summary
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This study will investigate OC-001 as monotherapy, and in combination with an anti-Programmed Cell Death Protein-1 (PD-1) or anti-Programmed Cell Death Ligand-1 (PD-L1) Antibody inhibitor, in various cancer types

Official Title
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A Phase 1b/2a Two-Part, Open-Label, Multicenter Study to Evaluate the Safety and Pharmacokinetics of OC-001 as Monotherapy and in Combination With an Anti-PD-1/Anti-PD-L1 Antibody in Patients With Selected Locally Advanced or Metastatic Cancers

Conditions
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Cancer, Neoplasms, Metastatic Cancer, Triple Negative Breast Cancer, Gastric Cancer, Cervical Cancer, Ovarian Cancer, Hepatocellular Carcinoma, Squamous Cell Carcinoma of Head and Neck, Urothelial Carcinoma, Urothelial Neoplasm, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Locally Advanced Solid Tumor, Locally Advanced Malignant Neoplasm, Squamous Cell Carcinoma, Sarcoma, Merkel Cell Carcinoma, Bladder Cancer

Intervention / Treatment
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* Drug: OC-001
* Drug: OC-001 in Combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histological or cytological evidence of a diagnosis of selected cancer types that is locally advanced and/or metastatic Have the presence of evaluable disease for the Phase 1b part of the study Have the presence of evaluable and measurable disease for the Phase 2a part of the study The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their disease or patients who have refused standard treatments. Cancer treatment and type criteria: Have received at least 1 but no more than 4 prior systemic therapies for locally advanced or metastatic disease (e.g., hormonal, cytotoxic, etc.) for the following cancer types, for Phase 1b: Triple Negative Breast Cancer (TNBC): Must have recurrent/refractory TNBC, defined as any breast cancer that expresses less than (˂)1% estrogen receptor (ER), ˂ 1% progesterone receptor (PR), and is Human Epidermal Growth Factor Receptor 2 (Her2) negative. Must have failed at least one chemotherapy regimen. Gastric Cancer: Must have failed a platinum-containing chemotherapy regime. Cervical Cancer: Must have failed at least one chemotherapy regimen. Ovarian Cancer: Must have failed a platinum-containing chemotherapy regimen but not be platinum refractory. Hepatocellular Cell Carcinoma (HCC): May have failed unlimited liver local therapies. Sarcoma: Must have failed at least one prior chemotherapy regimen. Squamous Cell Carcinoma of Head and Neck (SCCHN): Must have failed a platinum-containing chemotherapy regiment. Must have failed a previous immune checkpoint inhibitor. Bladder Cancer: Must have failed a platinum-containing chemotherapy regiment. Must have failed a previous immune checkpoint inhibitor. Non Small Cell Lung Cancer (NSCLC): Must have failed a platinum-containing chemotherapy regimen or Immuno Oncology (IO) agent in the first line. Must have failed a previous immune checkpoint inhibitor. Must not have any history of tumors that test positive for epidermal growth factor receptor (EGFR), Receptor Tyrosine Kinase (ROS1) , Anaplastic Lymphoma Kinase (ALK) mutations or ALK fusions or any other mutations for which tyrosine kinase inhibitors are available. Renal Cell Carcinoma (RCC): Must have failed at least one prior systemic therapy. Must have failed a previous IO agent. Urothelial Cancer: Must have failed at least one prior systemic therapy. Must have failed a previous IO agent. Merkel Cell: Must have failed at least 1 prior systemic therapy for advanced disease and may have failed a previous IO agent. Squamous Cell Carcinoma of the Skin: Must have failed at least 1 prior systemic therapy for advanced disease and may have failed a previous IO agent. For Phase 2a: Must have histological or cytological confirmation of a solid tumor that is locally advanced or metastatic. At least one cancer type will be selected amongst the ones evaluated in the Phase 1b part of the study. Have adequate organ function Have a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Have discontinued cytotoxic therapy, biologic therapy, immunotherapy, radiotherapy, and cancer-related hormonal therapy at least 21 days prior to study enrollment Are recovered or recovering from the acute adverse effects of any chemotherapy, biologic, therapy, immunotherapy, cancer-related hormonal therapy, or radiotherapy Patients who have had major surgery must be fully recovered and greater than (≥)4 weeks post-operative Men with partners of child-bearing potential or women with child-bearing potential must agree to use a medically approved contraceptive method during and for at least 12 weeks following the last dose of study drug (e.g., intrauterine device (IUD), birth control pills, or barrier method) Women of child-bearing potential must have a negative serum pregnancy test documented Have an estimated life expectancy of at least 3 months Exclusion Criteria: Have symptomatic central nervous system (CNS) metastasis. Patients with treated CNS metastases are eligible for this study if they are asymptomatic and off of corticosteroids for a minimum of 7 days. Patients with primary brain tumors are not eligible Have a history of major organ transplant (e.g., heart, lungs, liver, and kidney) or an autologous or allogeneic hematopoietic stem cell transplant Females who are pregnant or nursing Have known, symptomatic acquired immuno deficiency syndrome (AIDS) or active hepatitis A, B or C Previous treatment-related, severe (≥Grade 3) Adverse Event (AE) or any neurologic or ocular AE while receiving an IO agent Active or prior documented autoimmune disease within the past 2 years Patients with vitiligo, Grave's disease or psoriasis not requiring systemic treatment within the past 2 years are eligible Active or prior documented inflammatory bowel disease History of tuberculosis, interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required corticosteroid therapy Receipt of live attenuated vaccination within 28 days prior Current or prior use of immunosuppressive medication within 28 days prior Are currently enrolled in another clinical study of an investigational medicinal product Have a second primary malignancy that may affect the interpretation of results Are unwilling or unable to participate in, or do not have tissue adequate for a tumor biopsy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug: Dose Escalation<br>Escalating doses of OC-001 administered intravenously (IV) | Drug: OC-001<br>* Monotherapy in Phase 1b<br>|
| Experimental: Drug: Combination: Tumor Type 1<br>Doses of OC-001 administered by IV in combination anti-PD-1 or anti-PD-L1 Antibody (Ab) | Drug: OC-001 in Combination<br>* Anti-PD-1/anti-PD-L1 Ab administered per approved prescribing schedule, in Phase 2a<br>|
| Experimental: Drug: Combination: Tumor Type 2<br>Doses of OC-001 administered by IV in combination anti-PD-1 or anti-PD-L1 Antibody (Ab) | Drug: OC-001 in Combination<br>* Anti-PD-1/anti-PD-L1 Ab administered per approved prescribing schedule, in Phase 2a<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with a Dose Limiting Toxicity (DLT) in Phase 1b | A Dose-Limiting Toxicity (DLT) is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the criteria identified in the Common Terminology Criteria for Adverse Events (CTCAE, Version 5) | Baseline through Cycle 1 (Day 28) | 
| Number of participants with any Serious Adverse Event or Treatment-Emergent Adverse Event in Phase 2a | Number of participants with any Serious Adverse Event or Treatment-Emergent Adverse Event in Phase 2a | Baseline up to two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the OC-001 Plasma Concentration Time Curve (AUC) in Phase 1b | After single and multiple dose administration | Baseline through 12 weeks | 
| Maximum Observed OC-001 Concentration (Cmax) in Phase 1b | After single and multiple dose administration | Baseline through 12 weeks | 
| Time to reach OC-001 Cmax (Tmax) in Phase 1b | Time of maximum concentration observed | Baseline through 12 weeks | 
| Minimum Observed OC-001 Concentration (Cmin) in Phase 1b | After single and multiple dose administration | Baseline through 12 weeks | 
| Overall Response Rate (ORR) in Phase 2a | In combination with an anti-PD-1 or anti-PD-L1 antibody | Baseline up to two years | 
| Progression Free Survival (PFS) in Phase 2a | In combination with an anti-PD-1 or anti-PD-L1 antibody | Baseline up to two years | 
| Duration of Response (DOR) in Phase 2a | In combination with an anti-PD-1 or anti-PD-L1 antibody | Baseline up to two years | 
| Time to Response (TTR) in Phase 2a | In combination with an anti-PD-1 or anti-PD-L1 antibody | Baseline up to two years | 
| Disease Control Rate (DCR) in Phase 2a | In combination with an anti-PD-1 or anti-PD-L1 antibody | Baseline up to two years | 
| Overall Survival (OS) in Phase 2a | In combination with an anti-PD-1 or anti-PD-L1 antibody | Baseline up to two years | 
| One-Year Survival Rate in Phase 2a | In combination with an anti-PD-1 or anti-PD-L1 antibody | Baseline up to two years | 
| Maximum Observed OC-001 Concentration (Cmax) in Phase 2a | In combination with an anti-PD-1 or anti-PD-L1 antibody | Baseline through 12 weeks | 
| Minimum Observed OC-001 Concentration (Cmin) in Phase 2a | In combination with an anti-PD-1 or anti-PD-L1 antibody | Baseline through 12 weeks |