Advanced Solid Tumors
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALIPH5201
Ascending dose levels of IPH5201 every 3 weeks (Q3W) for a maximum of 2 years
BIOLOGICALdurvalumab
Durvalumab Q3W for a maximum of 2 years
BIOLOGICALoleclumab
Oleclumab Q3W for a maximum of 2 years
Sponsors
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 101 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events as a measure of safety | From time of informed consent through treatment period and including the follow-up 12 weeks after last dose of investigational product, approximately 7 months | The primary endpoint is safety as assessed by the presence of adverse events (AEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs). |
| Incidence of clinically significant laboratory values as a measure of safety | From time of informed consent through 12 weeks after the last dose of investigational product, approximately 7 months | Number of subjects with clinically significant laboratory values from baseline including blood counts, liver, kidney and pancreas tests, electrolytes, and blood clotting. |
| Incidence of clinically significant electrocardiogram (ECG) abnormalities as a measure of safety | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum serum concentration (Cmax) of IPH5201 | From start of treatment through Cycle 6 (21 day cycle, approximately 5 months) | To characterize the pharmacokinetics of IPH5201 as monotherapy and in combination with durvalumab ± oleclumab |
| Area under the curve (AUC) of IPH5201 | From start of treatment through Cycle 6 (21 day cycle, approximately 5 months) | To characterize the pharmacokinetics of IPH5201 as monotherapy and in combination with durvalumab ± oleclumab |
| Serum trough concentrations (durvalumab) | From start of treatment through Cycle 6 (21 day cycle, approximately 5 months) | To determine the pharmacokinetics of durvalumab when administered in combination with IPH5201+/- oleclumab |
| OR (Objective Response; Response evaluation criteria in solid tumors [RECIST] v1.1) | From time of consent until date of first documented disease progression (approximately 4 months) | Evaluate the primary antitumor activity of IPH5201 monotherapy or in combination with durvalumab +/- oleclumab (disease control) |
| Incidence of antidrug antibodies (IPH5201) | From start of treatment until 90 days after end of treatment (approximately 7 months) | To determine the immunogenicity of IPH5201 as monotherapy and in combination with durvalumab ± oleclumab |
| Incidence of antidrug antibodies (durvalumab) | From start of treatment until 90 days after end of treatment (approximately 7 months) | To determine the immunogenicity of durvalumab in combination with IPH5201 ± oleclumab |
| Incidence of antidrug antibodies (oleclumab) | From start of treatment until 90 days after end of treatment (approximately 7 months) | To determine the immunogenicity of oleclumab in combination with IPH5201 + durvalumab |
| Serum trough concentrations (oleclumab) | From start of treatment through Cycle 6 (21 day cycle, approximately 5 months) | To determine the pharmacokinetics of oleclumab in combination with durvalumab and IPH5201 |
| DC (Disease Control; RECIST 1.1) | From time of consent until date of first documented disease progression (approximately 4 months) | Evaluate the primary antitumor activity of IPH5201 with durvalumab +/- oleclumab (disease control) |
| Half-life of IPH5201 | From start of treatment through Cycle 6 (21 day cycle, approximately 5 months) | To characterize the pharmacokinetics of IPH5201 as monotherapy and in combination with durvalumab ± oleclumab |
Countries
France, Spain, Switzerland, United States
Outcome results
None listed