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

Phase 1

Completed

• Conditions: Advanced Solid Tumors
• Interventions: Biological: IPH5201; Biological: durvalumab; Biological: oleclumab

• Registration Number: NCT04261075
• Lead Sponsor: MedImmune LLC

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.

Study Timeline

• Study First Submitted: 2020-01-07
• Study First Submitted QC: 2020-02-06
• Study First Posted: 2020-02-07
• Study Start: 2020-03-03
• Primary Completion: 2022-06-16
• Study Completion: 2022-06-16
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-12
• Last Update Posted: 2022-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 57

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
IPH5201 dose escalation with durvalumab	IPH5201	IPH5201 plus durvalumab
IPH5201 dose escalation with durvalumab + oleclumab	IPH5201	IPH5201 plus durvalumab and oleclumab
IPH5201 monotherapy dose escalation	IPH5201	IPH5201 monotherapy
IPH5201 dose escalation with durvalumab	durvalumab	IPH5201 plus durvalumab
IPH5201 dose escalation with durvalumab + oleclumab	durvalumab	IPH5201 plus durvalumab and oleclumab
IPH5201 dose escalation with durvalumab + oleclumab	oleclumab	IPH5201 plus durvalumab and oleclumab

Primary Outcome Measures

Name	Time	Method
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 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
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.

Secondary Outcome Measures

Name	Time	Method
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)
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
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
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)
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 (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
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 (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 (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
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

Trial Locations

Locations (1)

Research Site; 🇨🇭 Lausanne, Switzerland