Clinical trial NCT04261075: IPH5201 as Monotherapy or in Combination With Durvalumab +/- Oleclumab in Subjects With Advanced Solid Tumors.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2020-02-07
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events as a measure of safety
timeFrame: From time of informed consent through treatment period and including the follow-up 12 weeks after last dose of investigational product, approximately 7 months
measure: Incidence of clinically significant laboratory values as a measure of safety
timeFrame: From time of informed consent through 12 weeks after the last dose of investigational product, approximately 7 months
measure: Incidence of clinically significant electrocardiogram (ECG) abnormalities as a measure of safety
timeFrame: 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 outcomes:
measure: OR (Objective Response; Response evaluation criteria in solid tumors [RECIST] v1.1)
timeFrame: From time of consent until date of first documented disease progression (approximately 4 months)
measure: DC (Disease Control; RECIST 1.1)
timeFrame: From time of consent until date of first documented disease progression (approximately 4 months)
measure: Half-life of IPH5201
timeFrame: From start of treatment through Cycle 6 (21 day cycle, approximately 5 months)
measure: Maximum serum concentration (Cmax) of IPH5201
timeFrame: From start of treatment through Cycle 6 (21 day cycle, approximately 5 months)
measure: Area under the curve (AUC) of IPH5201
timeFrame: From start of treatment through Cycle 6 (21 day cycle, approximately 5 months)
measure: Serum trough concentrations (durvalumab)
timeFrame: From start of treatment through Cycle 6 (21 day cycle, approximately 5 months)
measure: Serum trough concentrations (oleclumab)
timeFrame: From start of treatment through Cycle 6 (21 day cycle, approximately 5 months)
measure: Incidence of antidrug antibodies (IPH5201)
timeFrame: From start of treatment until 90 days after end of treatment (approximately 7 months)
measure: Incidence of antidrug antibodies (durvalumab)
timeFrame: From start of treatment until 90 days after end of treatment (approximately 7 months)
measure: Incidence of antidrug antibodies (oleclumab)
timeFrame: From start of treatment until 90 days after end of treatment (approximately 7 months)
Other outcomes:
Locations:
city: Huntersville
country: United States
facility: Research Site
state: North Carolina
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Bordeaux Cedex
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
Study officials:
References: