MEDI9447 Alone and in Combination With MEDI4736 in Adult Participants With Select Advanced Solid Tumors.

MedImmune

Status and phase: Completed; Phase 1

Conditions: Solid Tumors

Treatments: Drug: Oleclumab; Drug: Durvalumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02503774

D6070C00001

Details and patient eligibility

About

The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination with MEDI4736 in Adult Participants with Select Advanced Solid Tumors

Enrollment: 192 patients

Sex: All

Ages: 18 to 101 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult participants; age ≥ 18
• Written and signed informed consent must be obtained
• Have histologic or cytologic documentation of solid tumor including EGFRm NSCLC
• Participants must have at least 1 lesion that is measurable using RECIST guidelines
• Participants must consent to provide archived tumor specimens or tumor biopsies for correlative biomarker studies.
• Eastern Cooperative Oncology Group performance score of 0 or 1
• Adequate organ function

Exclusion criteria

• Prior treatment with tumor necrosis factor receptor superfamily agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR). One cohort also excludes anti CTLA-4, PD-L1, and anti PD-L1.

• Participants who have received prior therapy with regimens containing CTLA-4, PD-L1, or PD-1 antagonists may be permitted to enroll under certain conditions

• Cardiac or peripheral vascular disease meeting any of the following criteria:

  • Past history of myocardial infarction in the prior 12 months
  • Past history of stroke or transient ischemic attack requiring medical therapy
  • Congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification

• Grade 3 or greater edema (eg, peripheral, pulmonary)

• History of Grade 3 or greater thromboembolic events in the prior 12 months

• Participants with active tuberculosis are ineligible. In settings where there is clinical or radiographic evidence of tuberculosis, active disease must be ruled out

• Active or prior documented autoimmune or inflammatory disorders

• Untreated central nervous system (CNS) metastatic disease

• Known positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or active hepatitis A or C

• Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, ductal carcinoma in situ of the breast that has been surgically cured

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, uncontrolled hypertension, uncontrolled diabetes, or psychiatric illness/social situations that would limit compliance with study requirement

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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192 participants in 11 patient groups

Dose-escalation: Oleclumab Dose 1

Experimental group

Description:

Participants will receive oleclumab Dose 1 intravenously (IV) every two weeks (Q2W) until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Oleclumab

Dose-escalation: Oleclumab Dose 2

Experimental group

Description:

Participants will receive oleclumab Dose 2 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Oleclumab

Dose-escalation: Oleclumab Dose 3

Experimental group

Description:

Participants will receive oleclumab Dose 3 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Oleclumab

Dose-escalation: Oleclumab Dose 4

Experimental group

Description:

Participants will receive oleclumab Dose 4 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Oleclumab

Dose-escalation: Oleclumab Dose 1 + Durvalumab Dose 1

Experimental group

Description:

Participants will receive oleclumab Dose 1 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Durvalumab

Drug: Oleclumab

Dose-escalation: Oleclumab Dose 2 + Durvalumab Dose 1

Experimental group

Description:

Participants will receive oleclumab Dose 2 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Durvalumab

Drug: Oleclumab

Dose-escalation: OleclumabDose 3 + Durvalumab Dose 1

Experimental group

Description:

Participants will receive oleclumab Dose 3 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Durvalumab

Drug: Oleclumab

Dose-escalation: OleclumabDose 4 + Durvalumab Dose 1

Experimental group

Description:

Participants will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Durvalumab

Drug: Oleclumab

Dose-expansion (CRC): Oleclumab Dose 4 + Durvalumab Dose 1

Experimental group

Description:

Participants with previously treated microsatellite stable-colorectal cancer (MSS-CRC) will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Durvalumab

Drug: Oleclumab

Dose-expansion (Pancreatic adenocarcinoma): Oleclumab Dose 4+ Durvalumab Dose 1

Experimental group

Description:

Participants with previously treated pancreatic adenocarcinoma will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Durvalumab

Drug: Oleclumab

Dose-expansion (NSCLC): Oleclumab Dose 4 + Durvalumab Dose 1

Experimental group

Description:

Participants with previously treated EGFRm NSCLC will receive oleclumab Dose 4 IV followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Treatment:

Drug: Durvalumab

Drug: Oleclumab