A Phase I, First-in-Human Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of VIR-5500 (AMX-500) in Participants With Prostate Cancer
Study Identifier:
VIR-5500-V101
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
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Study Summary
The study will be conducted in 4 parts and will commence with dose escalation of AMX-500 as a monotherapy (Part 1), followed by monotherapy dose expansion (Part 2). Part 1 (Monotherapy Dose Escalation): Single-agent AMX-500 dose escalation Part 2 (Monotherapy Dose Expansion): Single-agent AMX-500 dose expansion To assess the safety, pharmacokinetics and preliminary efficacy of VIR-5500 in combination with androgen receptor pathway inhibitors in first-line mCRPC To assess the safety, pharmacokinetics, and preliminary efficacy of VIR-5500 in participants with metastatic castration-resistant prostate cancer (mCRPC).
Objectives were to characterize safety, pharmacokinetics (PK) profiles, anti-tumor activity, and determine the dose(s)/regimen(s) for expansion.
To assess the safety, pharmacokinetics and preliminary ecacy of VIR-5500 in both early and late-line metastatic castration-resistant prostate cancer (mCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC)
To measure the safety and efficacy of VIR-5500 monotherapy in late-line mCRPC, and of VIR-5500 in combination with an androgen receptor pathway inhibitor (ARPI) in early-line mCRPC and mHSPC.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Prostate
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Male
Age
18+ years
Study Drug
Drug: Experimental: Part 1: VIR-5500 Monotherapy Dose Escalation
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
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 imagingHave 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 apartNodal or visceral progression as defined by RECIST v1.1 with PCWG3 modificationsAppearance of ≥ 2 new lesions in bone scanHave been treated with ≥ 1 second-generation androgen-signaling inhibitor, including abiraterone, apalutamide, darolutamide, and/or enzalutamideHave been treated with ≥ 1 prior taxane regimens (example (e.g.), docetaxel, cabazitaxel) in either mHSPC or mCRPC settingParticipants 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 therapyAre 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 imagingHave 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 apartNodal or visceral progression, as defined by RECIST v1.1 with PCWG3 modificationsAppearance of ≥ 2 new lesions in bone scanHave 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 settingHave been treated with ≥ 1 second-generation androgen-signaling inhibitor, including abiraterone, apalutamide, darolutamide, and/or enzalutamideHave been treated with ≥ 1 prior taxane regimens (e.g., docetaxel, cabazitaxel) in either mHSPC or mCRPC settingParticipants 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 therapyInclusion 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 allowedNo prior exposure to taxane-based chemotherapy or other cytotoxic agents, including antibody-drug conjugates (ADCs) administered specifically for the treatment of mCRPCParticipants 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 therapyHave metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imagingHave 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 apartNodal or visceral progression, as defined by RECIST v1.1 with PCWG3 modificationsAppearance of ≥ 2 new lesions in bone scanHave 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-sensitiveMetastatic 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 eligibleParticipants 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 MRIHigh-volume disease is defined as: Presence of visceral metastases OR 4 bone lesions, with ≥1 beyond the vertebral bodies and pelvisParticipant 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 dosingInclusion 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 intentPSA doubling time ≤ 12 months at the time of study entryScreening 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 cancerScreening serum testosterone > 150 ng/dLInclusion Criteria Specific to Part 1a (Japanese Participants with mCRPC)
- Participant is of Japanese descent and will be participating at a site in JapanHave metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imagingHave 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 apartNodal or visceral progression as defined by RECIST v1.1 with PCWG3 modificationsAppearance of ≥ 2 new lesions in bone scanHave been treated with ≥ 1 second-generation androgen-signaling inhibitor, including but not limited to abiraterone, apalutamide, darolutamide, and/or enzalutamideHave been treated with ≥ 1 prior taxane regimens (e.g., docetaxel, cabazitaxel) in either the mHSPC or mCRPC settingPrior treatment with PSMA-targeted radioligand therapy, immunotherapy, sipuleucel-T, PARP inhibitors, and radium-223 is allowedParticipants 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 therapyInclusion Criteria Specific to Part 2a (Chinese Participants with mCRPC)
- Participant is of Chinese descent and will be participating at a site in ChinaHave metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imagingHave 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 apartNodal or visceral progression as defined by RECIST v1.1 with PCWG3 modificationsAppearance of ≥ 2 new lesions in bone scanHave been treated with ≥ 1 second-generation androgen-signaling inhibitor, including but not limited to abiraterone, apalutamide, darolutamide, and/or enzalutamideHave been treated with ≥ 1 prior taxane regimens (e.g., docetaxel, cabazitaxel) in either the mHSPC or mCRPC settingPrior treatment with PSMA-targeted radioligand therapy, immunotherapy, sipuleucel-T, PARP inhibitors, and radium-223 is allowedParticipants 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 componentsHave acute or chronic infectionsHave 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 meningitisHave lesions in proximity of vital organsApplicable to mHSPC cohorts only:
- Any prior treatment with a GnRH analogue or ARSIAny prior anticancer pharmacotherapy or surgery for metastatic prostate cancerExclusion 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 inhibitorHave a history or presence of clinically relevant CNS pathology within 12 months of enrollmentHave had significant cardiovascular disease within the last 3 monthsExclusion 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 screeningCurrently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Juan Francisco Rodriguez
Status
Recruiting
Condition(s) Treated at Site
Prostate