Trial of LAVA-1207 in Patients With Therapy Refractory Metastatic Castration Resistant Prostate Cancer

Study Overview
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Brief Summary
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This is a phase 1/2a, first-in-human study to evaluate the safety and tolerability of LAVA-1207 in patients with therapy refractory metastatic castration resistant prostate cancer

Detailed Description
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This trial is an open-label Phase 1 and 2a dose escalation trial with an expansion cohort to investigate the safety and tolerability of LAVA-1207 in patients with therapy refractory mCRPC.

Official Title
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Phase 1/2a Open-label Trial to Evaluate the Safety, Tolerability, PK, PD, Immunogenicity, and Antitumor Activity of LAVA-1207, a PSMA-targeting Bispecific γδ-T Cell Engager, in Patients With Therapy Refractory mCRPC

Conditions
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Metastatic Castration Resistant Prostate Cancer

Intervention / Treatment
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* Biological: LAVA-1207


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Patient must be 18 years of age inclusive or above, at the time of signing the informed consent. Male patient with mCRPC with measurable or evaluable disease Patient should have failed at least 1 line of taxane-based chemotherapy Patient should have received a 2nd generation or later androgen receptor targeted therapy/ androgen biosynthesis inhibitor Patients with evidence of progressive disease Predicted life-expectancy of ≥ 6 months. ECOG performance status of 0 or 1. Males who are: Surgically sterile Compliant with an effective contraceptive regimen (i.e. use of male condom with female partner and assuring use of an additional highly effective contraceptive method with a failure rate Capable of giving signed and dated informed consent prior to initiation of any trial-related procedures EXCLUSION CRITERIA Uncontrolled or severe intercurrent medical condition. Patient has any active-, uncontrolled-, or suspected infection. Known clinically relevant immunodeficiency disorders. Unstable cardiovascular function Previous treatment with an aminobisphosphonate IV (e.g. ibandronate, pamidronate, zoledronate etc) within 4 weeks prior to initial IMP. Known ongoing drug and alcohol abuse in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LAVA-1207<br>In part 1 (dose escalation) LAVA-1207 will be administered via intravenous infusion with dose escalation In part 2 (dose expansion) patients will receive LAVA-1207 at the dose established in part 1 of the study | Biological: LAVA-1207<br>* In part 1 & part 2 LAVA-1207 will be administered via intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 & Part 2: Frequency and severity of AEs | Frequency and severity of Adverse Events using the Common Terminology Criteria and grading for Adverse Events | Approximately 6 months | 
| Part 1: Frequency and type of DLT | A DLT is defined as an adverse event that is unrelated to disease progression, intercurrent illness, or concomitant medications and is occurring during the first 28 days of treatment. | First 28 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 & Part 2: Number of participants with an antitumor response | According to immune Response Evaluation Criteria in Solid Tumors (iRECIST) | Approximately 6 months | 
| Part 1 & Part 2: Pharmacokinetic of LAVA-1207, area under the concentration versus time curve (AUC) | Area under the plasma concentration versus time curve (AUC) of LAVA-1207 will be assessed in all patients | Approximately 6 months | 
| Part 1 & Part 2: Incidence and prevalence of anti-LAVA-1207 antibodies | Development of antibodies (anti-drug antibodies) to LAVA-1207 will be evaluated | Approximately 6 months | 
| Part 1 & Part 2: Biomarkers, binding of LAVA-1207 to Vγ9Vδ2-T cells | Binding of LAVA-1207 to Vγ9Vδ2-T cells will be measured in whole blood | Approximately 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, PSMA, mCRPC, Phase 1 dose escalation, Phase 1 safety, Phase 2 safety, open-label