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

• ClinicalTrials.gov Identifier: NCT04261075
• Recruitment Status: Completed
• First Posted: February 7, 2020
• Last Update Posted: August 15, 2022
• Sponsor: MedImmune LLC
• Information provided by (Responsible Party): MedImmune LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors	Biological: IPH5201; Biological: durvalumab; Biological: oleclumab	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 3, 2020
• Actual Primary Completion Date: June 16, 2022
• Actual Study Completion Date: June 16, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events as a measure of safety [ Time Frame: 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).
2. Incidence of clinically significant laboratory values as a measure of safety [ Time Frame: 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.
3. Incidence of clinically significant electrocardiogram (ECG) abnormalities as a measure of safety [ Time Frame: 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 Outcome Measures :

1. OR (Objective Response; Response evaluation criteria in solid tumors [RECIST] v1.1) [ Time Frame: 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)
2. DC (Disease Control; RECIST 1.1) [ Time Frame: 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)
3. Half-life of IPH5201 [ Time Frame: 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
4. Maximum serum concentration (Cmax) of IPH5201 [ Time Frame: 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
5. Area under the curve (AUC) of IPH5201 [ Time Frame: 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
6. Serum trough concentrations (durvalumab) [ Time Frame: 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
7. Serum trough concentrations (oleclumab) [ Time Frame: 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
8. Incidence of antidrug antibodies (IPH5201) [ Time Frame: 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
9. Incidence of antidrug antibodies (durvalumab) [ Time Frame: 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
10. Incidence of antidrug antibodies (oleclumab) [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 101 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, North Carolina

Research Site

Huntersville, North Carolina, United States, 28078

United States, Rhode Island

Research Site

Providence, Rhode Island, United States, 02906

United States, Tennessee

Research Site

Nashville, Tennessee, United States, 37203

France

Research Site

Bordeaux Cedex, France, 33076

Research Site

Villejuif, France, 94805

Spain

Research Site

Barcelona, Spain, 8035

Research Site

Madrid, Spain, 28027

Switzerland

Research Site

Lausanne, Switzerland, 1011

Sponsors and Collaborators

MedImmune LLC

More Information

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT04261075
• Other Study ID Numbers: D6770C00001
• First Posted: February 7, 2020
• Last Update Posted: August 15, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Durvalumab; Antineoplastic Agents, Immunological; Antineoplastic Agents