Testing the Drug Adavosertib With or Without an Immunotherapy in People With Advanced Cancers That Have DNA Repair Changes - CHARM2

About the Study

This clinical trial is studying whether a targeted drug called adavosertib — given alone or together with an immunotherapy drug called pembrolizumab — is safe and may help shrink or control advanced cancers that have changes in their DNA repair pathways. These DNA repair defects make the cancer cells more dependent on certain pathways and may make them more sensitive to these drugs.

• Adavosertib is a medicine that blocks a protein (WEE1) that cancer cells use to repair damaged DNA and survive.

• Pembrolizumab (an anti-PD-1 antibody) is a type of immunotherapy that helps the immune system recognize and attack cancer cells.

Researchers want to learn whether adavosertib alone or combined with pembrolizumab is more effective at slowing tumor growth in people whose tumors have specific genetic changes that affect DNA repair.

What the Study Involves

If a person joins this study:

• They will be randomly placed into one of two treatment groups:

  • Group 1: Adavosertib alone

  • Group 2: Adavosertib plus pembrolizumab

• Treatment is given in repeated cycles that include taking adavosertib by mouth and receiving pembrolizumab through intravenous infusion (for people in group 2).

• Participants will have regular clinic visits for medicine administration, medical exams, blood tests, and imaging scans to check for side effects and see how the cancer is responding.

• Treatment will continue as long as it is safe and shows benefit; participants will also have follow-up visits to monitor long-term outcomes.

This study is open to:

Adults (age 18 and older) who:

• Have advanced (metastatic or unresectable) solid tumors that are no longer responding to treatments.

• Have certain DNA repair gene defects — for example, changes in genes such as BRCA1, BRCA2, ATM, PALB2, CHEK2, FANCA, or other related genes — as confirmed by prior genetic testing of the tumor or blood.

• Are willing to take study medication and attend clinic visits for treatment, tests, and scans.

Additional inclusion criteria can be found here. 

This study is not open to:

People who:

• Are younger than 18 years old.

• Have a medical condition that would make it unsafe to take the study drugs (such as certain serious heart, liver, or lung conditions).

• Are pregnant or breastfeeding.

• Are receiving other investigational treatments that could interfere with this study.

Additional exclusion criteria can be found here.