A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors

The study consists of 3 parts: dose escalation (Part 1), dose expansion (Part 2), and dose
exploration (Part 3). Part 1 will evaluate dose escalation of durvalumab in combination with
monalizumab in adult subjects with select advanced solid tumor malignancies. Part 2 will
evaluate further the identified dose of durvalumab in combination with monalizumab from Part
1 in adult subjects with select advanced solid tumor malignancies. Part 3 will evaluate dose
exploration of durvalumab in combination with monalizumab and standard of care systemic
therapy with or without biological agent, and monalizumab in combination with biological
agent in adult subjects with CRC.

Inclusion Criteria:

1. Subjects must have histologic documentation of advanced recurrent or metastatic
cancer.

2. Subjects must be at the recurrent/metastatic setting, with selected advanced solid
tumors.

3. Subjects must have at least one lesion that is measurable by RECIST v1.1

4. Part 3, Dose exploration, CRC subjects can be treatment naïve but should not have
received more than two line of systemic therapy in the recurrent/metastatic setting.

Exclusion Criteria

1. Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may
be permitted upon discussion with the medical monitor.

2. Prior participation in clinical studies that include durvalumab alone or in
combination, where the study has registrational intent and the analyses for the
primary endpoint have not yet been completed

3. Receipt of any conventional or investigational anticancer therapy within 4 weeks prior
to the first dose of study treatment

4. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer
treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.