Description
There are many treatment options for men with various stages of prostate cancer. Some treatments work well for a while but can cause medical problems in some men. Also, the cancer may come back after treatment.
This is an early development study of VIR-5500 in men with prostate cancer. In this study, VIR-5500 will be given to people for the first time. VIR-5500 will either be given by itself or given together with one or more standard cancer treatments: enzalutamide, darolutamide and docetaxel. Some other cancer treatments may also be given with VIR-5500 during this study, depending on results from other ongoing studies.
Early development studies are mostly about safety, but also to find the most suitable dose. Other aims are to check if VIR-5500 shows signs of reducing tumor growth and to learn how the body processes VIR-5500. This will be done both for VIR-5500 given by itself and given together with the other cancer treatments.
The main aim(s) of the study are to check the safety of different doses of VIR-5500 when given by itself and given together with the standard cancer treatments, and how well it is tolerated; to find a suitable dose of VIR-5500 when given by itself and given together with the standard cancer treatments; to check the safety of VIR-5500 when given by itself to people in China and Japan; and to check how well VIR-5500 controls tumors when given by itself and given together with the standard cancer treatments.
Adult men with certain types of advanced prostate cancer can take part. Their cancer has spread to other parts of the body (metastatic). The different types of cancer in this study are: Metastatic hormone-sensitive prostate cancer (mHSPC). Prostate cancer that needs testosterone to grow; Metastatic castration-resistant prostate cancer (mCRPC). Prostate cancer that continues to grow even when testosterone levels are low; and High-risk biochemical recurrent prostate cancer (high-risk BRPC). Biochemical recurrence is a rise in PSA levels after treatment for prostate cancer. Men whose PSA levels double in less than 1 year are considered high risk of the cancer coming back and quickly getting worse.
In this study, VIR-5500 will be given to people for the first time. VIR-5500 will either be given itself or given together with at least one of the standard cancer treatments: enzalutamide, darolutamide, and docetaxel. The standard cancer treatment given will depend on which part of the study the men are in, and what type of prostate cancer they have. Other cancer treatments may be given, depending on results from other ongoing studies.
The study will have 4 parts.
In Part 1, different small groups of men with Metastatic castration-resistant prostate cancer (mCRPC) will receive lower to higher doses of VIR-5500 given by itself. Any medical problems will be recorded for each dose. This is to find out suitable doses to use in Part 2 of the study.
In Part 2, other small groups of men with mCRPC will receive the suitable doses of VIR-5500 worked out from Part 1. These men will have previously received specific cancer treatments before starting this study.
In Part 3, other different small groups of men with metastatic hormone-sensitive prostate cancer (mHSPC), mCRPC or high-risk BRPC will receive lower to higher doses of VIR-5500 given by itself or given with the other standard cancer treatments. They will be given VIR-5500 with enzalutamide or darolutamide, VIR-5500 with docetaxel, VIR-5500 with docetaxel and enzalutamide, or VIR- 5500 with docetaxel and darolutamide. Any medical problems will be recorded for each dose. This is to find out suitable doses to use in Part 4 of the study.
In Part 4, other small groups of men with mHSPC, mCRPC or high-risk biochemical recurrent prostate cancer (BRPC) will receive the suitable doses of VIR-5500 given together with the standard cancer treatments, worked out in Part 3. They will be given VIR-5500 with enzalutamide, VIR-5500 with darolutamide, VIR-5500 with docetaxel and enzalutamide, or VIR-5500 with docetaxel and darolutamide. The standard cancer treatment given will depend on their previous treatment before joining the study and the type of prostate cancer they have.
Eligibility criteria
Inclusion Criteria:
Inclusion Criteria Applicable to mCRPC Cohorts in Part 1 and PSMA-Targeted Radioligand-Naive mCRPC Cohort (Part 2 Cohort 2-2)
* Have metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan imaging
* Have had prior bilateral orchiectomy and/or are receiving androgen deprivation therapy (ADT) and have a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L)
* Have documented progressive mCRPC based on ≥ 1 of the following criteria (per PCWG3):
* PSA level ≥ 1 ng/mL that has increased on ≥ 2 successive occasions ≥ 1 week apart
* Nodal or visceral progression as defined by RECIST v1.1 with PCWG3 modifications
* Appearance of ≥ 2 new lesions in bone scan
* Have been treated with ≥ 1 second-generation androgen-signaling inhibitor, including abiraterone, apalutamide, darolutamide, and/or enzalutamide
* Have been treated with ≥ 1 prior taxane regimens (example (e.g.), docetaxel, cabazitaxel) in either mHSPC or mCRPC setting
* Participants with known mutations in BRCA1/2 must have received a PARP inhibitor if an approved therapy is locally available, and participant is considered suitable for this therapy
* Are deemed unsuitable for standard of care (Only applicable for Part 1)
Inclusion Criteria Applicable for PSMA-Targeted Radioligand-Experienced mCRPC Cohort Only (Part 2 Cohort 2-1)
* Have metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging
* Have documented progressive disease (PD) based on ≥ 1 of the following criteria (per PCWG3):
* PSA level ≥ 1 ng/mL that has increased on ≥ 2 successive occasions ≥ 1 week apart
* Nodal or visceral progression, as defined by RECIST v1.1 with PCWG3 modifications
* Appearance of ≥ 2 new lesions in bone scan
* Have had prior bilateral orchiectomy and/or are receiving ADT and have a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L)
* Have received PSMA-targeted radioligand-based therapy, such as 177Lu-PSMA-617 in any setting
* Have been treated with ≥ 1 second-generation androgen-signaling inhibitor, including abiraterone, apalutamide, darolutamide, and/or enzalutamide
* Have been treated with ≥ 1 prior taxane regimens (e.g., docetaxel, cabazitaxel) in either mHSPC or mCRPC setting
* Participants with known mutations in BRCA1/2 must have received a PARP inhibitor if an approved therapy is locally available, and participant is considered suitable for this therapy
Inclusion Criteria Applicable for 1L/2L Taxane-Naïve mCRPC Cohorts Only (Cohort 2-3, Part 3, Cohort 4a-1, and Cohort 4b-1)
* Prior treatment with ARSI (including but not limited to abiraterone, enzalutamide, darolutamide, or apalutamide). Participants without prior ARSI treatment in the mCRPC setting are also allowed
* No prior exposure to taxane-based chemotherapy or other cytotoxic agents, including antibody-drug conjugates (ADCs) administered specifically for the treatment of mCRPC
* Participants with known mutations in BRCA1/2 must have received a PARP inhibitor if an approved therapy is locally available, and participant is considered suitable for this therapy
* Have metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging
* Have documented PD based on ≥ 1 of the following criteria (per PCWG3):
* PSA level ≥ 1 ng/mL that has increased on ≥ 2 successive occasions ≥ 1 week apart
* Nodal or visceral progression, as defined by RECIST v1.1 with PCWG3 modifications
* Appearance of ≥ 2 new lesions in bone scan
* Have had prior bilateral orchiectomy and/or are receiving ADT and have a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L)
Inclusion Criteria Applicable for mHSPC Cohorts Only (Part 3, Cohort 4a-2, and Cohort 4b-2)
* Histologically documented prostate adenocarcinoma which is de novo or recurrent and considered castration-sensitive
* Metastatic disease prior to first dose, with clear evidence of ≥ 1 bone lesion (defined as one lesion with positive uptake on bone scan) and/or ≥ 1 soft tissue lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment with CT and/or MRI. Participants with metastatic disease identified by PSMA-PET only, will not be eligible. Participants with disease limited to regional pelvic lymph nodes only are not eligible
* Participants should have high-risk OR high-volume disease per the following criteria:
* High-risk is defined as presence of at least 2 of the following: Gleason score of greater than or equal to (≥) 8; presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis on CT or MRI
* High-volume disease is defined as: Presence of visceral metastases OR 4 bone lesions, with ≥1 beyond the vertebral bodies and pelvis
* Participant is receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy starting ≥ 14 days and \< 4 months prior to first dose with no radiographic evidence of disease progression or rising PSA levels prior to first day of dosing
Inclusion Criteria Applicable for High-Risk BRPC Cohorts Only (Dose Optimization, Part 3a, and Part 4a-3)
* Have BRPC defined by meeting all of the following criteria:
* Prostate cancer initially treated by radical prostatectomy or radiotherapy (including brachytherapy) or both, with curative intent
* PSA doubling time ≤ 12 months at the time of study entry
* Screening PSA ≥ 1 ng/mL in patients who have had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir in patients who had radiotherapy only as primary treatment for prostate cancer
* Screening serum testosterone \> 150 ng/dL
Inclusion Criteria Specific to Part 1a (Japanese Participants with mCRPC)
* Participant is of Japanese descent and will be participating at a site in Japan
* Have metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging
* Have had prior bilateral orchiectomy and/or are receiving an ADT and have a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L)
* Have documented progressive mCRPC based on ≥ 1 of the following criteria (per PCWG3:
* PSA level ≥ 1 ng/mL that has increased on ≥ 2 successive occasions ≥ 1 week apart
* Nodal or visceral progression as defined by RECIST v1.1 with PCWG3 modifications
* Appearance of ≥ 2 new lesions in bone scan
* Have been treated with ≥ 1 second-generation androgen-signaling inhibitor, including but not limited to abiraterone, apalutamide, darolutamide, and/or enzalutamide
* Have been treated with ≥ 1 prior taxane regimens (e.g., docetaxel, cabazitaxel) in either the mHSPC or mCRPC setting
* Prior treatment with PSMA-targeted radioligand therapy, immunotherapy, sipuleucel-T, PARP inhibitors, and radium-223 is allowed
* Participants with known mutations in BRCA1/2 must have received a PARP inhibitor if an approved therapy is locally available, and participant is considered suitable for this therapy
Inclusion Criteria Specific to Part 2a (Chinese Participants with mCRPC)
* Participant is of Chinese descent and will be participating at a site in China
* Have metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging
* Have had prior bilateral orchiectomy and/or are receiving ADT and have a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L)
* Have documented progressive mCRPC based on ≥ 1 of the following criteria (per PCWG3):
* PSA level ≥ 1 ng/mL that has increased on ≥ 2 successive occasions ≥ 1 week apart
* Nodal or visceral progression as defined by RECIST v1.1 with PCWG3 modifications
* Appearance of ≥ 2 new lesions in bone scan
* Have been treated with ≥ 1 second-generation androgen-signaling inhibitor, including but not limited to abiraterone, apalutamide, darolutamide, and/or enzalutamide
* Have been treated with ≥ 1 prior taxane regimens (e.g., docetaxel, cabazitaxel) in either the mHSPC or mCRPC setting
* Prior treatment with PSMA-targeted radioligand therapy, immunotherapy, sipuleucel-T, PARP inhibitors, and radium-223 is allowed
* Participants with known mutations in BRCA1/2 must have received a PARP inhibitor if an approved therapy is locally available, and participant is considered suitable for this therapy
Exclusion Criteria:
* Have dominant histopathological features representative of sarcomatoid, spindle cell, or neuroendocrine small cell components
* Have acute or chronic infections
* Have a concomitant medical or inflammatory condition that may increase the risk of toxicity to VIR-5500 (AMX-500)
* Have known active CNS metastases and/or carcinomatous meningitis
* Have lesions in proximity of vital organs
Applicable to mHSPC cohorts only:
* Any prior treatment with a GnRH analogue or ARSI
* Any prior anticancer pharmacotherapy or surgery for metastatic prostate cancer
Exclusion Criteria Applicable to Part 3a and Part 4a Only: VIR-5500 (AMX-500) in Combination With an ARSI (Enzalutamide or Darolutamide)
* Are progressing rapidly while taking a second-generation androgen-signaling inhibitor
* Have a history or presence of clinically relevant CNS pathology within 12 months of enrollment
* Have had significant cardiovascular disease within the last 3 months
Exclusion Criteria Applicable to Part 3b and Part 4b Only: VIR-5500 (AMX-500) in Combination With Docetaxel ± ARSI
* Abnormal liver function test (LFT) values during screening
* Currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study