Summary

This is a Phase 2, multicenter, two-stage, open-label, parallel-group study designed to
evaluate the efficacy and safety of vudalimab (XmAb20717) in patients with selected advanced
gynecologic and genitourinary malignancies.

Objectives

This is a Phase 2, multicenter, two-stage, open-label, parallel-group study designed to
evaluate the efficacy and safety of vudalimab in patients with selected advanced gynecologic
and genitourinary malignancies and to identify tumor types for further evaluation.

In Stage 1, subjects will be enrolled into 1 of 5 tumor-specific, parallel cohorts (n = 10
each):

- Platinum-resistant high-grade serous ovarian cancer (HGSOC)

- Chemotherapy relapsed or refractory clear cell ovarian, endometrial, or peritoneal
cancer

- Immune-checkpoint-inhibitor-refractory microsatellite stable (MSS) endometrial cancer
(EC)

- Previously treated recurrent or metastatic cervical cancer

- High-risk metastatic castration-resistant prostate cancer (mCRPC)

Within each tumor-specific cohort in Stage 1, a primary endpoint of ORR at 12 weeks, based on
investigator review, will be used to determine cohort expansion into Stage 2. Each Stage 1
cohort that achieves an ORR of = 20% (at least 2 out of 10 subjects with an objective
response) will enroll up to an additional 20 subjects in Stage 2. Cohorts with an ORR of less
than 20% will discontinue enrollment. However, additional factors will be considered in
determining an expansion into Stage 2 (eg, enrollment rate, complete versus partial response,
and DOR).

Eligibility

1. Able to provide written informed consent
2. Adult (age = 18 years)
3. Cancer must have progressed after treatment with all approved and medically appropriate therapies or have no appropriate available therapies
4. Histologically confirmed diagnosis of one of the following tumor types, along with clinical/pathologic confirmation of the additional requirements for each indication, as appropriate:
5. Persistent or recurrent clear cell carcinoma of the ovary, peritoneum, or endometrium after treatment with platinum-based systemic chemotherapy
6. Persistent or recurrent high-grade serous carcinoma of the ovary, fallopian tube, or peritoneum after treatment with platinum-based systemic chemotherapy (except subjects with a diagnosis of carcinosarcoma)
7. Recurrent or metastatic cervical carcinoma previously treated with standard-of-care systemic chemotherapy and FDA-approved immunotherapy, if eligible
8. Advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) in patients who are not candidates for curative surgery or radiation, and that has progressed following treatment with no more than one prior line of systemic therapy and prior treatment with FDA-approved combination therapy consisting of a checkpoint inhibitor and a targeted agent
9. High-risk metastatic castration-resistant prostate cancer:
10. Castration resistance defined as progressive disease after surgical castration, or progression in the setting of medical androgen ablation with a castrate level of testosterone (< 50 ng/dL)
11. High-risk disease is any visceral, soft tissue, or lymph node metastasis(es) with/without bone metastases
12. Measurable disease by Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
13. Adequate available archival formalin-fixed paraffin-embedded block(s)/slides containing tumor and/or adequate predose fresh tumor biopsy tissue
14. Eastern Cooperative Oncology Group performance status of 0 or 1
15. Female subjects of childbearing potential must agree to use a highly effective method of birth control during and for 4 weeks after completion of study. Women are considered to be of childbearing potential unless it is documented that they are over the age of 60 OR postmenopausal by history with no menses for 1 year and confirmed by follicle-stimulating hormone (using local reference ranges) OR have a history of hysterectomy and/or bilateral oophorectomy OR have a history of bilateral tubal ligation. Highly effective methods of birth control include hormonal birth control (oral, intravaginal, or transdermal), or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or intrauterine), intrauterine devices (IUDs), intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner (provided partner is the sole sexual partner and there has been a medical assessment of surgical success), or sexual abstinence
16. Fertile male subjects must be willing to practice a highly effective method of birth control during and for 4 weeks after completion of study
17. Male subjects must agree not to donate sperm from screening through 4 weeks after completion of study
18. Able and willing to complete the entire study according to the study schedule

Treatment Sites in Georgia