A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors

MedImmune

Status and phase: Active, not recruiting; Phase 1

Conditions: Selected Advanced Solid Tumors

Treatments: Drug: Pemetrexed; Drug: Paclitaxel or Nab-Paclitaxel; Biological: MEDI5752; Drug: Carboplatin; Biological: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03530397

2018-003075-35 (EudraCT Number)

D7980C00001

Details and patient eligibility

About

The purpose of this study is to evaluate MEDI5752 and carboplatin and pemetrexed or paclitaxel or nab-paclitaxel in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.

Full description

This is a phase 1, first-time-in-human, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety and tolerability, and efficacy, pharmacokinetics and Immunogenicity of MEDI5752 and carboplatin and pemetrexed or paclitaxel or nab-paclitaxel in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.

Enrollment: 401 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Age ≥ 18 years at the time of screening
2. World Health Organization/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
3. Life expectancy ≥ 12 weeks
4. Histologically or cytologically-confirmed advanced solid tumors
5. Subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy or any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment may be eligible to enter the study following a washout period as applicable
6. Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception
7. Nonsterilized males who are sexually active with a female partner of childbearing potential must use a male condom with spermicide where locally available from Day 1 and for 90 days after the final dose of investigational product. Males receiving pemetrexed or carboplatin must use contraception during study treatment and up to 6 months thereafter.
8. Subjects must have at least one measurable lesion
9. Adequate organ and marrow function
10. Written informed consent and any locally required authorization
11. Subjects must provide tumor material as applicable

Exclusion Criteria

1. Involvement in the planning and/or conduct of the study (applies to both MedImmune staff and/or staff at the study site)

2. Concurrent enrollment in another clinical study, unless it is an observational clinical study or the follow-up period of an interventional study

3. For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4:

   1. Subjects must not have received anti-PD-1, anti-PD-L1, anti-CTLA-4 or any other immunotherapy or immune-oncology (IO) agent within 21 days of commencing treatment with investigational product.
   2. Subject must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
   3. All AEs while receiving prior immunotherapy must have completely resolved or resolved to Grade 1 prior to screening for this study.

4. Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product is excluded.

5. Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product.

6. Active or prior documented autoimmune or inflammatory disorders

7. History of active primary immunodeficiency:

8. History of organ transplant

9. Known allergy or reaction to any component of the planned study treatment.

10. Untreated CNS metastatic disease, leptomeningeal disease, or cord compression

11. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria

12. Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of Investigational Product or still recovering from prior surgery

13. Female subjects who are pregnant or breastfeeding, as well as male or female subjects of reproductive potential who are not willing to employ one highly effective method of birth control

14. Uncontrolled intercurrent illness, that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent.

15. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of the subject's safety or study results

16. Judgment by the investigator that the subject is unsuitable to participate in the study and the subject is unlikely to comply with study procedures, restrictions, and requirements.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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401 participants in 3 patient groups

Arm A: MEDI5752

Experimental group

Description:

MEDI5752

Treatment:

Biological: MEDI5752

Arm B: MEDI5752 and chemotherapy

Experimental group

Description:

MEDI5752, pemetrexed, carboplatin and paclitaxel.

Treatment:

Drug: Carboplatin

Biological: MEDI5752

Drug: Paclitaxel or Nab-Paclitaxel

Drug: Pemetrexed

Arm C: Pembrolizumab and chemotherapy

Active Comparator group

Description:

pembrolizumab, pemetrexed, and carboplatin

Treatment:

Biological: Pembrolizumab

Drug: Carboplatin

Drug: Pemetrexed