A Study of DF6002 Alone and in Combination With Nivolumab

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, drug-levels, drug-effects and preliminary anti-tumor activity of DF6002 alone and in combination with Nivolumab in participants with advanced solid tumors.

Official Title
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A Phase 1/2, First-In-Human, Multi-Part, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of DF6002 as a Monotherapy and in Combination With Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: DF6002
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced/metastatic solid tumors, for which no standard therapy exists or standard therapy has failed among the following tumor types: melanoma, non-small cell lung cancer, small cell lung cancer, head and neck squamous cell, urothelial, gastric, esophageal, cervical, hepatocellular, merkel cell, cutaneous squamous cell carcinoma, renal cell, endometrial, triple-negative breast, ovarian, and prostate ECOG performance status of 0 or 1 Clinical or radiological evidence of disease Adequate hematological, hepatic and renal function Anticoagulants are required for the following: Khorana Risk Score ≥ 2 or as assessed by Investigator as being at high risk for venous thromboembolism (VTE) or history of VTE ≥ 6 months from enrollment Exclusion Criteria: Concurrent anticancer treatment (with the exception of palliative bone directed radiotherapy), immune therapy, or cytokine therapy (except for erythropoietin), major surgery (excluding prior diagnostic biopsy), concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of study treatment Previous malignant disease other than the current target malignancy within the last 3 years, with the exception of basal or squamous cell carcinoma of the skin, localized prostate cancer or cervical carcinoma in situ Rapidly progressive disease Serious cardiac illness or medical conditions Known diagnosis of antiphospholipid syndrome or clinically significant hereditary thrombophilia Other protocol-defined inclusion/exclusion criteria apply

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy Dose Escalation<br> | Drug: DF6002<br>* Specified dose on specified days<br>|
| Experimental: Monotherapy Dose Expansion (Melanoma)<br> | Drug: DF6002<br>* Specified dose on specified days<br>|
| Experimental: Monotherapy Dose Expansion (NSCLC)<br> | Drug: DF6002<br>* Specified dose on specified days<br>|
| Experimental: Combination Dose Escalation<br> | Drug: DF6002<br>* Specified dose on specified days<br>Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Combination Dose Expansion (Melanoma)<br> | Drug: DF6002<br>* Specified dose on specified days<br>Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Combination Dose Expansion (NSCLC)<br> | Drug: DF6002<br>* Specified dose on specified days<br>Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose-limiting toxicities (DLTs) | Phase 1/1b only | During the first 3 weeks of treatment | 
| Overall Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per an Independent Endpoint Review Committee (IERC) | Phase 2 only | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment emergent adverse events (TEAEs) |  | Up to 2 years | 
| Severity of TEAEs |  | Up to 2 years | 
| Duration of TEAEs |  | Up to 2 years | 
| Number of participants with changes from baseline in clinical laboratory parameters |  | Up to 2 years | 
| Number of participants with changes from baseline in electrocardiogram (ECG) parameters |  | Up to 2 years | 
| Number of participants with changes from baseline in vital sign parameters |  | Up to 2 years | 
| Number of participants with changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance status |  | Up to 2 years | 
| Duration of Response (DOR) according to RECIST 1.1 per Investigator assessment |  | Up to month 24 | 
| Area under the plasma concentration-time curve from the time of dosing to the time of the last observation (AUC 0-T) |  | Up to day 28 | 
| Area under the plasma concentration-time curve from the time of dosing extrapolated to infinity (AUC 0-INF) |  | Up to day 28 | 
| Maximum serum concentration observed post-dose (Cmax) |  | Up to day 28 | 
| Best overall response (BOR) according to RECIST 1.1 per Investigator assessment |  | Approximately one year | 
| Clinical benefit rate (CBR) according to RECIST 1.1 per Investigator assessment |  | Up to 2 years | 
| Confirmed ORR per RECIST 1.1 per Investigator assessment | Phase 1/1b only | Up to 2 years | 
| Progression-free survival (PFS) according to RECIST 1.1 per Investigator assessment | Phase 2 only | Up to 2 years | 
| CBR according to RECIST 1.1 per IERC | Phase 2 only | Up to 2 years | 
| PFS according to RECIST 1.1 per IERC | Phase 2 only | Up to 2 years | 
| DOR according to RECIST 1.1 per IERC | Phase 2 only | Up to month 24 | 
| Unconfirmed response after 4 cycles according to RECIST 1.1 | Phase 2 only | Up to 2 years | 
| Overall Survival (OS) | Phase 2 only | Up to 5 years | 
| Serum titers of anti-DF6002 antibodies | Phase 2 only | Up to 2 years | 
| Serum titers of anti-nivolumab antibodies | Phase 2 only | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced or Metastatic Solid Tumors, Melanoma, Non-small Cell Lung Cancer, Nivolumab, DF6002 (BMS-986415)