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

NCT05369000 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: LAVA1207-001/LAVA1207-0022021-001789-39KEYNOTE-F73
• Study Type: interventional
• Target: 96
• Locations: 3 countries
• Sites: 12

Brief Summary

This is a phase 1, first-in-human study to evaluate Safety, Tolerability, PK, PD, Immunogenicity, and Antitumor Activity of LAVA-1207 alone or with low dose interleukin-2 or Pembrolizumab, in patients with therapy refractory metastatic castration resistant prostate cancer.

Conditions

Metastatic Castration Resistant Prostate Cancer

Keywords

prostate cancer; PSMA; mCRPC; Phase 1 dose escalation; Phase 1 safety; Phase 2 safety; open-label

Outcome Measures

Primary Outcomes (2)

• 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 and grading for CRS

  Approximately 24 months

• Part 1: Frequency and type of DLT

  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.illness, or concomitant medications and is occurring during the first 28 days of treatment.

  First 28 days of treatment

Secondary Outcomes (4)

• Part 1 & Part 2: Number of participants with an antitumor response

  Approximately 24 months

• Part 1 & Part 2: Pharmacokinetic of LAVA-1207, area under the concentration versus time curve (AUC)

  Approximately 6 months

• Part 1 & Part 2: Incidence and prevalence of anti-LAVA-1207 antibodies

  Approximately 6 months

• Part 1 & Part 2: Biomarkers, binding of LAVA-1207 to Vγ9Vδ2-T cells

  Approximately 24 months

Other Outcomes (1)

• Exploratory Objective

  Approximately 24 months

Study Arms (3)

LAVA-1207

EXPERIMENTAL

LAVA-1207

Biological: LAVA-1207

LAVA-1207 with Low-Dose Subcutaneous IL-2 (LDSC IL-2)

EXPERIMENTAL

LAVA-1207 with Low-Dose Subcutaneous IL-2 (LDSC IL-2)

Biological: LAVA-1207

LAVA-1207 plus Pembrolizumab

EXPERIMENTAL

LAVA-1207 plus Pembrolizumab

Biological: LAVA-1207; Biological: LAVA-1207 plus Pembrolizumab

Interventions

LAVA-1207 BIOLOGICAL

In part 1 \& part 2 • LAVA-1207 will be administered via intravenous infusion.

LAVA-1207; LAVA-1207 plus Pembrolizumab; LAVA-1207 with Low-Dose Subcutaneous IL-2 (LDSC IL-2)

LAVA-1207 plus Pembrolizumab BIOLOGICAL

Pembrolizumab will be administered via intravenous infusion

LAVA-1207 plus Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are eligible to be included in the arm only if all of the following criteria apply:
• Patient must be 18 years of age inclusive or above, at the time of signing the informed consent.
• 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.
• Patient should have failed at least 1 line of taxane-based chemotherapy or is deemed medically unsuitable to be treated with a taxane regimen.
• 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-mCRPC setting.
• Patient is unlikely to tolerate or derive clinically meaningful benefit from other available therapy.
• Patient for which any drug-related toxicity adverse effects of any prior cancer therapy have resolved to Grade 1 or less according to CTCAE version 5.0 or to baseline severity level (except for alopecia and peripheral neuropathy).
• Patients with evidence of progressive disease, defined as 1 or more of the following criteria:
• PSA level ≥1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart.
• Computed tomography (CT) or magnetic resonance imaging (MRI) scan: nodal or visceral progression as defined by RECIST 1.1.
• Bone scintigraphy: appearance of 2 or more new metastatic lesions.
• Patient should have undergone bilateral orchiectomy or should be on continuous androgen-deprivation therapy (ADT) with a gonadotropin-releasing hormone agonist or antagonist (surgical or medical castration).
• Total serum testosterone ≤ 50 ng/dL or 1.73 nmol/L.
• Evaluable (measurable or non-measurable) disease for prostate cancer.
• Predicted life-expectancy of ≥ 6 months.

You may not qualify if:

• Patients are excluded from the trial if any of the following criteria apply:
• Other malignancies within the last 2 years except adequately treated carcinoma in situ, basal or squamous cell skin carcinoma.
• Uncontrolled or severe intercurrent medical condition.
• Positive serological testing for human immunodeficiency virus (HIV) antibody.
• Positive serological hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) negative, and hepatitis C virus (HCV) 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.
• Patient has any active, uncontrolled, or suspected infection.
• Known clinically relevant immunodeficiency disorders.
• 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.
• 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.
• 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.
• 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.
• Treatment with other investigational agents in the 4 weeks prior to initial IMP administration.
• Major surgery within 4 weeks prior to initial IMP administration.
• Hypersensitivity to any of the excipients present in LAVA-1207 or IL-2 (if applicable).
• Previous treatment with any systemic immunosuppressant within 4 weeks prior to initial IMP administration, with the exception of systemic corticosteroid use up to oral dose of 10 mg prednisone daily (or equivalent for other steroids).

Sponsors & Collaborators

• Lava Therapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (12)

UCSF Medical Center at Parnassus

San Francisco, California, 94143, United States

Location

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Duke University Medical Center - Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

Location

Radboud Universiteit - Radboud Universitair Medisch Centrum (Radboudumc)

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

Erasmus MC (Erasmus Universitair Medisch Centrum Rotterdam)

Rotterdam, South Holland, 3000 CA, Netherlands

Location

Amsterdam UMC - VU Medisch Centrum (VUmc)

Amsterdam, 1081 HV, Netherlands

Location

ICO Hospitalet (Hospital Duran i Reynals)

Barcelona, 08908, Spain

Location

Hospital Universitartio 12 De Octubre

Madrid, 28041, Spain

Location

Centro Integral Oncologico Clara Campal (HM CIOCC)

Madrid, 28050, Spain

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Clinical Trials Management

  Lava Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2022
• First Posted: May 11, 2022
• Study Start: January 17, 2022
• Primary Completion: June 18, 2025
• Study Completion: June 18, 2025
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3); ES (3); US (6)