Prostate Cancer MedDRA version: 27.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: LAVA-1207
Product Code: NA
Pharmaceutical Form: Infusion
Other descriptive name: Humanised bispecific immunoglobulin VHH fragments against PSMA and Vgamma9Vdelta2 T-cell receptor
Concent
Sponsors
LAVA Therapeutics N.V.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Inclusion criteria (for patients treated with LAVA-1207 +/- LDSC IL-2): 1. Patient must be 18 years of age inclusive or above, at the time of signing the informed consent. 2. Male patient with mCRPC as defined by PCWG3 criteria (histologically confirmed adenocarcinoma; adenocarcinoma with =10% small-cell or neuroendocrine features is allowed). Brain metastasis are allowed as long as the patient’s symptoms are well controlled. 3. Patient should have failed at least 1 line of taxane-based chemotherapy or is deemed medically unsuitable to be treated with a taxane regimen. 4. Patient should have received a 2nd generation or later androgen receptor targeted therapy/ androgen biosynthesis inhibitor (e.g. abiraterone, enzalutamide, and/or apalutamide). Progression on novel antiandrogen therapy may have occurred in the non-metastatic CRPC setting. 5. Patients will be unlikely to tolerate or derive clinically meaningful benefit from other available therapy. 6. Patients for which any drug related toxicity adverse effects of any prior cancer therapy should have resolved to Grade 1 or less according CTCAE v5.0 or to baseline severity level (except for alopecia or peripheral neuropathy). 7. Patients has evidence of progressive disease, defined as 1 or more of the following criteria: a. PSA level =1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart. b. Computed tomography (CT) or magnetic resonance imaging (MRI) scan: nodal or visceral progression as defined by RECIST 1.1. c. Bone scintigraphy: appearance of 2 or more new metastatic lesions. 8. Patient should have undergone bilateral orchiectomy or should be on continuous androgendeprivation therapy (ADT) with a gonadotropin-releasing hormone agonist or antagonist (surgical or medical castration). 9. Total serum testosterone = 50 ng/dL or 1.73 nmol/L. 10. Evaluable (measurable or non-measurable) disease for prostate cancer. 11. Predicted life-expectancy of = 6 months. Inclusion criteria for LAVA-1207 plus pembrolizumab arm: 1. Patient must be 18 years of age inclusive or above, at the time of signing the informed consent. 2. Male patient with mCRPC as defined by PCWG3 criteria (histologically confirmed adenocarcinoma; adenocarcinoma with =10% small-cell or neuroendocrine features is allowed). Brain metastases are allowed as long as the patient's symptoms are well controlled, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 3. Patient should have failed at least 1 line of taxane-based chemotherapy or is deemed medically unsuitable to be treated with a taxane regimen. 4. Patient should have received a 2nd generation or later androgen receptor targeted therapy/androgen biosynthesis inhibitor (e.g. abiraterone, enzalutamide, and/or apalutamide). Progression on novel anti-androgen therapy may have occurred in the non-mCRPC setting. 5. Patient is unlikely to tolerate or derive clinically meaningful benefit from other available therapy. 6. Patient for which any drug-related toxicity adverse effects of any prior cancer therapy should have resolved to Grade 1 or less according CTCAE version 5.0 or to baseline severity level (except alopecia or peripheral neuropathy). 7. Patient has evidence of progressive disease, defined as 1 or more of the following c
Exclusion criteria
Exclusion criteria: Exclusion Criteria (for patients treated with LAVA-1207 +/- LDSC IL-2): 1. Other malignancies within the last 2 years except adequately treated carcinoma in situ, basal or squamous cell skin carcinoma. 2. Uncontrolled or severe intercurrent medical condition. 3. Positive serological testing for human immunodeficiency virus (HIV) antibody. 4. Positive serological hepatitis B surface antigen [HbsAg] and hepatitis B core antibody (anti-HBc) negative, and hepatitis C virus antibody. Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative polymerase chain reaction (PCR) within 6 weeks prior to initial IMP administration. Those who are PCR positive will be excluded. 5. Patient has any active, uncontrolled, or suspected infection. 6. Known clinically relevant immunodeficiency disorders. 7. A significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect participation in this trial. 8. Unstable cardiovascular function defined as: (a) symptomatic ischemia, or (b) uncontrolled clinically significant conduction abnormalities (i.e. ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block is not excluded), or (c) congestive heart failure New York Heart Association Class = 3, or (d) myocardial infarction within 3 months. 9. Previous treatment with antitumor therapies within 2 weeks prior to initial IMP for radiotherapy and androgen receptor targeted therapy/androgen biosynthesis inhibitor, and within 4 weeks for systemic chemotherapy or targeted immunotherapy. 10. Previous treatment with live or live attenuated vaccines within 2 weeks prior to initial IMP administration. New types of vaccines need to be evaluated as to their mode of action. 11. Treatment with other investigational agents in the 4 weeks prior to initial IMP administration. 12. Major surgery within 4 weeks prior to initial IMP administration. 13. Hypersensitivity to any of the excipients present in LAVA-1207 or IL-2 (if applicable). Exclusion Criteria for LAVA-1207 plus pembrolizumab arm: 1. Other malignancies within the last 2 years except adequately treated carcinoma in situ, basal or squamous cell skin carcinoma. 2. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV). Patients who are HbsAg negative and HBV viral DNA negative are eligible. Patients who had HBV but have received an antiviral treatment and show non-detectable viral DNA for 6 months are eligible. Patients who are seropositive because of HBV vaccine are eligible. 3. Seropositive for and with active viral infection with hepatitis C virus (HCV). Patients who had HCV but have received an antiviral treatment and show no detectable HCV viral DNA for 6 months are eligible. 4. History of allogenic tissue or solid organ transplant. 5. Positive serological testing for HIV. 6. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients. 7. Hypersensitivity to any of the excipients present in LAVA-1207. 8. Active infection requiring systemic therapy. 9. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 10. Has a diagnosis of immunodeficiency or is receiving chronic systemi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 Dose Escalation for LAVA-1207 alone, LAVA-1207 plus LDSC IL-2, and LAVA-1207 plus pembrolizumab. To investigate the safety and tolerability of treatment in patients with therapy refractory mCRPC. To determine the preliminary RP2D in patients with therapy refractory mCRPC for LAVA-1207 monotherapy, for LAVA-1207 + LDSC IL-2, and for LAVA-1207 + pembrolizumab. Part 2 To investigate the safety and tolerability at the RP2D in therapy refractory mCRPC patients with measurable and non-measurable refractory mCRPC patients with measurable and non-measurable disease. ;Secondary Objective: Part 1 Dose Escalation and Part 2 Expansion Cohort for LAVA-1207 alone, LAVA-1207 plus LDSC IL-2, and LAVA-1207 plus pembrolizumab • To explore the preliminary antitumor activity • To evaluate the pharmacokinetics of LAVA-1207. • To evaluate the pharmacodynamics of LAVA-1207. • To evaluate the immunogenicity of LAVA-1207.;Primary end point(s): Part 1 Dose Escalation for LAVA-1207 alone, LAVA-1207 plus LDSC IL-2, and LAVA-1207 plus pembrolizumab Frequency and severity of AEs using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and ASTCT grading for CRS. Frequency and type of DLT. Part 2 Expansion Cohort for LAVA-1207 alone and/or LAVA-1207 plus LDSC IL-2, and/or LAVA-1207 plus pembrolizumab Frequency and severity of AEs using the CTCAE version 5.0 and ASTCT grading of CRS at the RP2D.;Timepoint(s) of evaluation of this end point: Both for Part 1 and Part 2: Planned treatment duration is 24 weeks; this generally is sufficient to collect information to enable the assessment of the primary and secondary endpoints for both trial parts. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 Dose Escalation and Part 2 Expansion Cohort (for LAVA-1207 alone and/or LAVA-1207 plus LDSC IL-2 and/or LAVA-1207 plus pembrolizumab) Number of participants with an antitumor response according to immune response evaluation criteria in solid tumors (RECIST and iRECIST) in patients with measurable disease. Duration of response. Disease control rate (DCR) for patients with measurable disease at 8, 16 and 24 weeks. Number of participants who experience any PSA decrease, and number of participants who experience a PSA decrease of = 50% from baseline. Progression free survival (using Prostate Cancer Working Group 3 [PCWG3] for bone lesions and/or iRECIST criteria for soft-tissue lesions). Pharmacokinetic parameters. Pharmacodynamic markers. Incidence and prevalence of anti-LAVA-1207 antibodies;Timepoint(s) of evaluation of this end point: Both for Part 1 and Part 2: Planned treatment duration is 24 weeks; this generally is sufficient to collect information to enable the assessment of the primary and secondary endpoints for both trial parts. | — |
Countries
Netherlands, Spain, United States
Contacts
Public ContactClinical Operations
LAVA Therapeutics N.V.
Outcome results
None listed