LAVA1207-001/LAVA1207-002 A Phase 1 and 2a open-label trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of LAVA-1207, a PSMA-targeting bispecific γδ-T cell engager, alone or with low dose interleukin-2 or Pembrolizumab, in patients with therapy refractory metastatic castration resistant prostate cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

LAVA Therapeutics N.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Nov 2021 → 18 Jun 2025

Decision date (initial)

2024-08-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Lava Therapeutics N.V.

External identifiers

EU CT number

2024-515821-27-00

EudraCT number

2021-001789-39

ClinicalTrials.gov

NCT05369000

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety, Pharmacodynamic

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
Expansion Cohort for LAVA-1207 alone and/or LAVA-1207 plus LDSC IL2, and/or LAVA-1207 plus pembrolizumab.
To investigate the safety and tolerability at the RP2D in therapy
refractory mCRPC patients with measurable and non-measurable
disease.

Secondary objectives 1

1. 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 LAVA-1207. To evaluate the immunogenicity of LAVA-1207

Conditions and MedDRA coding

Prostate Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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 metastases 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-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 have resolved to Grade 1 or less according CTCAE version 5.0 or to baseline severity level (except for alopecia or peripheral neuropathy). 7. Patient 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 androgen-deprivation 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 criteria: a. PSA level ≥1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart. b. CT or 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 ADT with a gonadotropin-releasing hormone agonist or antagonist (surgical or medical castration).

Exclusion criteria 1

1. 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. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Part 1 * 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 * Frequency and severity of AEs using the CTCAE version 5.0 and ASTCT grading of CRS at the RP2D.

Secondary endpoints 1

1. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

LAVA Therapeutics N.V.

Sponsor organisation

LAVA Therapeutics N.V.

Address

Yalelaan 62

City

Utrecht

Postcode

3584 CM

Country

Netherlands

Scientific contact point

Organisation

LAVA Therapeutics N.V.

Contact name

Clinical Trials Administrator

Public contact point

Organisation

LAVA Therapeutics N.V.

Contact name

Clinical Trials Administrator

Third parties 6

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications