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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04261075
• Other study ID #: D6770C00001
• Status: Completed
• Phase: Phase 1
• Start date: March 3, 2020
• Est. completion date: June 16, 2022

Study information

• Verified date: August 2022
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: June 16, 2022
• Est. primary completion date: June 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 101 Years

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Biological:
• IPH5201
Ascending dose levels of IPH5201 every 3 weeks (Q3W) for a maximum of 2 years
• durvalumab
Durvalumab Q3W for a maximum of 2 years
• oleclumab
Oleclumab Q3W for a maximum of 2 years

Locations

Country	Name	City	State
France	Research Site	Bordeaux Cedex
France	Research Site	Villejuif
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Switzerland	Research Site	Lausanne
United States	Research Site	Huntersville	North Carolina
United States	Research Site	Nashville	Tennessee
United States	Research Site	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  France,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)