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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Biological: IPH5201; Biological: durvalumab; Biological: oleclumab

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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Bordeaux Cedex, France, 33076
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Spain
  • Barcelona, Spain, 8035
    • Research Site
  • Madrid, Spain, 28027
    • Research Site
• Switzerland
  • Lausanne, Switzerland, 1011
    • Research Site
• United States
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2020
• Primary Completion (Actual): June 16, 2022
• Study Completion (Actual): June 16, 2022

Study Registration Dates

• First Submitted: January 7, 2020
• First Submitted That Met QC Criteria: February 6, 2020
• First Posted (Actual): February 7, 2020

Study Record Updates

• Last Update Posted (Actual): August 15, 2022
• Last Update Submitted That Met QC Criteria: August 12, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: D6770C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No