(VELA) Study of BLU-222 in Advanced Solid Tumors

Inclusion Criteria:

1. Advanced solid tumors that has progressed beyond standard of care OR

2. HR+ HER2- BC that has progressed following treatment with a CDK4/6 inhibitor OR

3. Endometrial and gastric cancer that has progressed after at least 2 prior therapies (including one prior platinum therapy) OR

4. Platinum refractory or platinum resistant ovarian cancer CCNE1 amplified tumors thathave progressed beyond standard of care

Exclusion Criteria:

1. Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.

2. Have received the following anticancer therapy: a. Previous therapy with CDK2i, PKMYT1i, or WEE1i, except in Part 1A where up to 10patients who previously received PKMYT1i, or WEE1 inhibitor will be permitted.

3. Have central nervous system (CNS) metastases or spinal cord compression that isassociated with progressive neurological symptoms or requires increasing doses ofcorticosteroids to control the CNS disease.

4. Have known intracranial hemorrhage and/or bleeding diatheses.

5. Have clinically active ongoing ILD of any etiology, including drug-induced ILD, andradiation pneumonitis within 28 days prior to initiation of study treatment.

6. Have any unresolved toxicities from prior therapy greater than CTCAE Grade 1 or thathave not resolved to baseline at the time of starting the study.

7. Have mean resting QTcF > 450 msec in men or QTcF > 470 msec in women, a history ofprolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QTsyndrome.

8. Have clinically significant, uncontrolled, cardiovascular disease includingcongestive heart failure Grade III or IV according to the New York Heart Associationclassification; myocardial infarction or unstable angina within the previous 6months, uncontrolled hypertension, or clinically significant, uncontrolledarrhythmias, including bradyarrhythmia that may cause QT prolongation (eg, Type IIsecond degree heart block or third-degree heart block).

9. Have a history of another primary malignancy other than completely resectedcarcinomas in situ) that has been diagnosed or required therapy within 2 years priorto initiation of study treatment.

10. Have known active, uncontrolled infection (viral, bacterial, or fungal), includingtuberculosis, hepatitis B virus (HBV), hepatitis C virus, AIDS-related illness, orCOVID-19 infection (symptoms and a positive test result).

11. Requires treatment with a prohibited medication or herbal remedy that cannot bediscontinued at least 2 weeks before the start of study drug administration.

12. Have planned major surgical procedure within 14 days of the first dose of study drug (procedures such as central venous catheter placement, tumor needle biopsy, andfeeding tube placement are not considered major surgical procedures).

13. Unwilling or unable to comply with scheduled visits, study drug administration plan,laboratory tests, or other study procedures and study restrictions.

14. Patient is a woman who is not postmenopausal or surgically sterile, and is unwillingto abstain from sexual intercourse or employ highly effective contraception OR is aman who is not surgically sterile, and is unwilling to abstain from sexualintercourse or employ highly effective contraception

15. Patient is a pregnant female