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.

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.

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.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.