This study has been transitioned to CTIS with ID 2024-515821-27-00 check the CTIS register for the current data. Primary objectivesPart 1 Dose Escalation for LAVA-1207 alone, LAVA-1207 plus LDSC IL-2, and LAVA-1207 plus pembrolizumab• To investigate…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints
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.
Secondary outcome
Secondary endpoints
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.
Background summary
LAVA-1207 is an experimental treatment. LAVA-1207 is a bispecific humanized
antibody, developed in a laboratory and designed to help the immune system
fight cancer cells. LAVA-1207 binds to a particular protein called "PSMA",
which is found on the surface of tumor cells. By binding to it, LAVA-1207
activates the immune system to kill the tumor cells.
In this study, LAVA-1207 is administered to humans for the first time. It has
previously been tested in the lab, as well as on animals.
Study objective
This study has been transitioned to CTIS with ID 2024-515821-27-00 check the CTIS register for the current data.
Primary objectives
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, LAVA-1207 + LDSC IL-2, and LAVA-1207 + pembrolizumab.
Part 2 Expansion Cohort for LAVA-1207 alone, LAVA-1207 plus LDSC IL-2, and
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
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.
Study design
This trial is an open-label, multi-center, Phase 1 and 2a dose escalation trial
with an expansion cohort to investigate the safety, tolerability,
pharmacokinetics, pharmacodynamics, immunogenicity and preliminary antitumor
activity of LAVA-1207 in patients with therapy refractory mCRPC.
The trial will start with an open-label, dose-escalation part (Part 1) which
will include dose optimization to determine the preliminary RP2D with or
without LDSC IL-2.
Alternative dose schedules may be implemented, based on preliminary data
review, e.g., weekly administrations for LAVA-1207. An additional dose
escalation/expansion will be conducted with LAVA-1207 plus pembrolizumab
assuming safety data and preliminary antitumor activity data support expansion.
The second part of the trial (Part 2) will be an open-label expansion cohort at
the RP2D and schedule, in which the number of patients will be expanded to
confirm safety in a patient population with therapy refractory mCRPC with
measurable disease.
Intervention
LAVA-1207 is a concentrate for solution for infusion and will be administered
as IV infusion with a 14-day dosing interval. The infusion duration will be 2
hours in the first cycle, 1 hour in the 2nd cycle and 30 minutes in subsequent
cycles.
LDSC IL-2 will be administered as a single dose or as 3 daily doses starting at
24 hours (-1 hr- and +2 hrs) after the start of LAVA-1207 infusion for a total
duration of 4 cycles.
The study group receiving infusions of pembrolizumab will begin infusions every
6 weeks, starting with the second target dose of LAVA-1207.
In Part 2, patients will receive IV infusions of LAVA-1207 at the RP2D (dose
and schedule) as established in the dose escalation part of the trial (with- or
without LDSC IL-2).
Study burden and risks
Discomfort and Risks:
- Possible side effects of the treatment (possible) side effects are described
in the patient information
- Discomfort, pain, bruising: in rare cases infection, light-headedness /
fainting due to blood sampling
- Rash or irritation from ECG stickers.
- Following instructions related to study treatment and the visit schedule
Benefit:
It is possible that the study patient will benefit from the treatment but this
is not guaranteed.
Yalelaan 62
Utrecht 3584 CM
NL
Yalelaan 62
Utrecht 3584 CM
NL
Listed location countries
Age
Inclusion criteria
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.
Patients is unlikely to tolerate or derive clinically meaningful benefit from
other
available therapy.
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.
Exclusion criteria
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-515821-27-00 |
| EudraCT | EUCTR2021-001789-39-NL |
| CCMO | NL77530.056.21 |