IPH5201 as Monotherapy or in Combination With Durvalumab +/- Oleclumab in Subjects With Advanced Solid Tumors.

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability and to determine the dose of IPH5201 that can be used as monotherapy or in combination with durvalumab +/- oleclumab in subjects with advanced solid tumors.

Detailed Description
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Study D6770C00001 is a Phase 1, first-in-human, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, antitumor activity, pharmacokinetics, and immunogenicity of IPH5201 in adult subjects with advanced solid tumors, when administered as monotherapy or in combination with durvalumab ± oleclumab.

Official Title
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A Phase 1, First-in-Human, Multicenter, Open-label, Dose-escalation Study of IPH5201 as Monotherapy or in Combination With Durvalumab ± Oleclumab in Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Biological: IPH5201
* Biological: durvalumab
* Biological: oleclumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects; age ≥ 18 years Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Subjects diagnosed with advanced solid tumors. For Part 1 and Part 2 (IPH5201 in monotherapy or combined with durvalumab):Subjects must be refractory to standard therapy or for which no standard therapy exists. For Part 3 (IPH5201 combined with durvalumab and oleclumab): Subjects must have received and radiologically progressed on 1 prior line of systemic therapy for metastatic pancreatic ductal adenocarcinoma. Subjects must have at least 1 measurable lesion according to RECIST v1.1. Subjects must provide tumor specimens . Exclusion Criteria: Receipt of any conventional or investigational anticancer therapy (anti-CTLA-4, anti-PD-1, anti-PD-L1 antibodies) within 21 days of the planned first dose. Receipt of agents targeting CD73, CD39, or adenosine receptors. Concurrent enrollment in another therapeutic clinical study. Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent. No toxicity leading to permanent discontinuation of prior IO therapy Subjects must not have required the use of additional immunosuppression other than corticosteroids Active or prior documented autoimmune or inflammatory disorders within the past 5 years Cardiac and vascular criteria: Presence of myocardial infarction or unstable angina , or stroke, within 6 months. Congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension History of severe hypertension History of any grade of blood clot within 6 months Active infection, including tuberculosis; hepatitis B virus (HBV); hepatitis C virus (HCV); or human immunodeficiency virus (HIV) Uncontrolled illness including certain lung diseases, uncontrolled diabetes, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study. Other invasive malignancy within 2 years. Major surgery within 28 days prior to first dose Female subjects who are pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 101 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPH5201 monotherapy dose escalation<br>IPH5201 monotherapy | Biological: IPH5201<br>* Ascending dose levels of IPH5201 every 3 weeks (Q3W) for a maximum of 2 years<br>|
| Experimental: IPH5201 dose escalation with durvalumab<br>IPH5201 plus durvalumab | Biological: IPH5201<br>* Ascending dose levels of IPH5201 every 3 weeks (Q3W) for a maximum of 2 years<br>Biological: durvalumab<br>* Durvalumab Q3W for a maximum of 2 years<br>|
| Experimental: IPH5201 dose escalation with durvalumab + oleclumab<br>IPH5201 plus durvalumab and oleclumab | Biological: IPH5201<br>* Ascending dose levels of IPH5201 every 3 weeks (Q3W) for a maximum of 2 years<br>Biological: durvalumab<br>* Durvalumab Q3W for a maximum of 2 years<br>Biological: oleclumab<br>* Oleclumab Q3W for a maximum of 2 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events as a measure of safety | The primary endpoint is safety as assessed by the presence of adverse events (AEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs). | From time of informed consent through treatment period and including the follow-up 12 weeks after last dose of investigational product, approximately 7 months | 
| Incidence of clinically significant laboratory values as a measure of safety | Number of subjects with clinically significant laboratory values from baseline including blood counts, liver, kidney and pancreas tests, electrolytes, and blood clotting. | From time of informed consent through 12 weeks after the last dose of investigational product, approximately 7 months | 
| Incidence of clinically significant electrocardiogram (ECG) abnormalities as a measure of safety | 12 lead ECGs will be measured to identify clinical significant abnormalities including ECGs that demonstrate a QTcF value >500ms, 2 additional 12-lead ECGs should be obtained over a 30 minute time period to confirm prolongation based on the average QTcF value | From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximatley 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OR (Objective Response; Response evaluation criteria in solid tumors [RECIST] v1.1) | Evaluate the primary antitumor activity of IPH5201 monotherapy or in combination with durvalumab +/- oleclumab (disease control) | From time of consent until date of first documented disease progression (approximately 4 months) | 
| DC (Disease Control; RECIST 1.1) | Evaluate the primary antitumor activity of IPH5201 with durvalumab +/- oleclumab (disease control) | From time of consent until date of first documented disease progression (approximately 4 months) | 
| Half-life of IPH5201 | To characterize the pharmacokinetics of IPH5201 as monotherapy and in combination with durvalumab ± oleclumab | From start of treatment through Cycle 6 (21 day cycle, approximately 5 months) | 
| Maximum serum concentration (Cmax) of IPH5201 | To characterize the pharmacokinetics of IPH5201 as monotherapy and in combination with durvalumab ± oleclumab | From start of treatment through Cycle 6 (21 day cycle, approximately 5 months) | 
| Area under the curve (AUC) of IPH5201 | To characterize the pharmacokinetics of IPH5201 as monotherapy and in combination with durvalumab ± oleclumab | From start of treatment through Cycle 6 (21 day cycle, approximately 5 months) | 
| Serum trough concentrations (durvalumab) | To determine the pharmacokinetics of durvalumab when administered in combination with IPH5201+/- oleclumab | From start of treatment through Cycle 6 (21 day cycle, approximately 5 months) | 
| Serum trough concentrations (oleclumab) | To determine the pharmacokinetics of oleclumab in combination with durvalumab and IPH5201 | From start of treatment through Cycle 6 (21 day cycle, approximately 5 months) | 
| Incidence of antidrug antibodies (IPH5201) | To determine the immunogenicity of IPH5201 as monotherapy and in combination with durvalumab ± oleclumab | From start of treatment until 90 days after end of treatment (approximately 7 months) | 
| Incidence of antidrug antibodies (durvalumab) | To determine the immunogenicity of durvalumab in combination with IPH5201 ± oleclumab | From start of treatment until 90 days after end of treatment (approximately 7 months) | 
| Incidence of antidrug antibodies (oleclumab) | To determine the immunogenicity of oleclumab in combination with IPH5201 + durvalumab | From start of treatment until 90 days after end of treatment (approximately 7 months) |