This study has been transitioned to CTIS with ID 2023-506541-39-00 check the CTIS register for the current data. Monotherapy (Parts A, B*, D, E, F and G)Primary Objectives - Evaluate the safety and tolerability of Tarlatamab - Part A only: Determine…
ID
Source
Brief title
Condition
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Monotherapy:
For all indications:
Primary Endpoints • Dose limiting toxicities (DLTs), treatment-emergent adverse
events (AEs), treatment-related AEs, and clinically significant changes in
vital signs, ECG, physical examinations, and clinical laboratory tests
Combination Therapy:
Primary Endpoints:
For subjects with RR SCLC who progressed or recurred following at least 1
platinum based regimen:
o DLTs), treatment-emergent AEs, treatment-related AEs, and clinically
significant changes in vital signs, ECG, physical examinations, and clinical
laboratory tests
Please see protocol section 1 for more information.
Secondary outcome
Monotherapy:
Secondary Endpoints
- Objective Response (OR) per modified Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1
- Duration of Response (DOR)
- Time to response (TTR)
- Progression-Free Survival (PFS)
- Overall Survival (OS)
For subjects with ED SCLC with ongoing clinical benefit following no more than
6 cycles of platinum-based chemotherapy only:
- Relapse Free Survival (RFS)
Combination Therapy:
Secondary Endpoints:
For subjects with RR SCLC who progressed or recurred following at least 1
platinum based regimen:
o PK parameters for Tarlatamab following intravenous administration including
but not limited to Cmax, Cmin, AUC over the dosing interval, accumulation
following multiple dosing, and, if feasible, t1/2
o OR per modified RECIST 1.1
o DOR
o TTR
o PFS
o OS
Please see section 1 of the protocol for more information.
Background summary
Small Cell Lung Cancer (SCLC), accounting for 10-15% of lung cancer (Rudin et
al, 2015), is an aggressive lung cancer subtype with neuroendocrine
differentiation and strongly associated with smoking (Koinis et al, 2016). It
displays a distinct natural history characterized by a high growth fraction,
rapid doubling time and early establishment of widespread metastatic lesions
(Gustafsson et al, 2008). While 30% of patients present with disease confined
to one hemithorax [limited disease (LD)], the majority of cases have disease
not encompassed by one radiotherapy field [extended disease (ED)]. SCLC is
exquisitely sensitive to first-line chemotherapy (approximately 60%-70%
response rates) and to radiation which is stark contrast to subsequent
resistance to second-line and subsequent therapies after disease recurrence
(Byers et al, 2015). Patients with ED develop drug resistance and die as a
result of disease at a median time of 10 to 12 months from diagnosis (Rudin et
al, 2015). For patients with ED SCLC, first-line treatment is platinum-based
chemotherapy. Most patients in the United States receive platinum-etoposide
(EP) chemotherapy (with either carboplatin or cisplatin), and some patients
receive platinum-irinotecan as an alternative, especially outside the United
States. After relapse, topotecan is the only second-line drug approved by the
US Food and Drug Administration (FDA). However, despite its indication in this
setting, topotecan has produced disappointing response rates (Byers et al,
2015).
Study objective
This study has been transitioned to CTIS with ID 2023-506541-39-00 check the CTIS register for the current data.
Monotherapy (Parts A, B*, D, E, F and G)
Primary Objectives
- Evaluate the safety and tolerability of Tarlatamab
- Part A only: Determine the MTD or RP2D of Tarlatamab
Secondary Objectives
• Evaluate preliminary anti-tumor activity of Tarlatamab
• Characterize the pharmacokinetics of Tarlatamab
Exploratory Objectives
- Evaluate immunogenicity of Tarlatamab
- Evaluate protein, nucleic acid and cellular biomarkers in blood pre and post
Tarlatamab treatment (eg cytokines, lymphocyte status, CTCs)
- Evaluate relationship of baseline target protein expression in tumor tissue,
tumor microenvironment characteristics and clinical benefit
- Evaluate the effects of chemotherapy and time elapsed post chemotherapy on *T
cell fitness* (Part B only)
- Evaluate relationship of cytokine release syndrome (CRS) mitigation
strategies and the incidence of CRS (Part D only)
Combination Therapy (Part C)
Primary Objectives
For subjects with RR SCLC who progressed or recurred following at least 1
platinum based regimen:
• Evaluate the safety and tolerability of Tarlatamab when administered in
combination with pembrolizumab
• Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
of Tarlatamab in combination with pembrolizumab
Secondary Objectives
For subjects with RR SCLC who progressed or recurred following at least 1
platinum based regimen:
• Characterize the PK of Tarlatamab when administered in combination with
pembrolizumab
• Evaluate preliminary anti-tumor activity of Tarlatamab in combination with
pembrolizumab
Please refer to protocol section 1 for more information.
Study design
This is an open-label, ascending, multiple dose, phase 1 study evaluating
Tarlatamab monotherapy and in combination with anti PD1 therapy in subjects
with SCLC. Tarlatamab will be administered (with or without step dosing) as a
short term IV infusion as part of a 4-week cycle Parts A-F, and as part of a
3-week cycle in Part G.
The study will consist of 7 parts:
• Part A (monotherapy): For subjects with RR SCLC who progressed after at least
1 platinum-based regimen, which includes 2 phases: (A1) Dose Exploration and
(A2) Dose Expansion. Part A3 will be conducted in China to confirm Part A1
MTD/RP2D.
• Part B (monotherapy): For subjects with ED SCLC with ongoing clinical benefit
following no more than 6 cycles of platinum-based chemotherapy. Part B was
planned to commence once MTD or RP2D is identified in Part A in subjects with
RR SCLC. Part B will not be opened.
• Part C (combination with anti PD1 therapy): Tarlatamab in combination with
anti-PD1 therapy for subjects with RR SCLC who progressed after at least 1
platinum-based regimen which includes: Dose exploration of Tarlatamab in
combination with fixed dose of pembrolizumab
• Part D (evaluation of additional CRS mitigation strategies): Tarlatamab
monotherapy for subjects with RR SCLC who progressed after at least 1
platinum-based regimen. To mitigate the risk of CRS, one or more of the
following prophylactic measures may be implemented (during cycle 1 only): IV
hydration, additional corticosteroid prophylaxis with oral dexamethasone,
administration of tocilizumab prophylaxis, etanercept prophylaxis, or
acetaminophen prophylaxis.
• Part E (Tarlatamab administration with 24-hour monitoring): This cohort will
allow for subjects to have Tarlatamab administered in
inpatient or at outpatient infusion centers with 20 to 24 hours monitoring for
cycle 1 doses.
• Part F (Tarlatamab 8-hour outpatient cohort): In Part F, up to 30 subjects
will be enrolled to evaluate the safety and tolerability of Tarlatamab when
administered in outpatient infusion centers with 8-hour monitoring for cycle 1
doses (discharge between 6-8 hours is acceptable.
• Part G (Tarlatamab alternative dosing schedule cohort[s]): This part will
explore different dosing schedules of Tarlatamab in subjects with RR SCLC.
The dose exploration phases of the study Part A1 will estimate the MTD or RP2D
of Tarlatamab using a Bayesian logistic regression model (BLRM; Neuenschwander
et al, 2008). Once a RP2D has been determined for Tarlatamab monotherapy in
Part A1, this will be followed by dose expansion phase (Part A2) to confirm
the RP2D and to obtain further safety and efficacy data.
Please see protocol section 3.1 for more information.
Intervention
Tarlatamab will be administered as an IV infusion for 60 minutes followed by a
flush at dose levels detailed in Table 1-1 and 1-2 of the protocol.
Study burden and risks
The risks and potential side effects of Tarlatamab and the procedures performed
in this study are fully described in the Informed Consent Form. Tarlatamab may
cause all, some, or none of the side effects listed below. These side effects
can be mild but could also be serious life-threatening or even result in death.
Because this is the first time Tarlatamab is being given to humans, it is
unknown if the patient will have any side effects. Side effects, such as
pituitary changes were seen in animals. The meaning of these findings to humans
is uncertain. Disadvantages of participation in the study may be: • The
additional time it will take • Additional or longer hospital stays • Additional
tests • Instructions the patient needs to follow • possible side effects /
complications of study related tests or procedures • possible adverse effects /
discomforts from the study drug It is uncertain if taking part in this study
will be beneficial for the patient. The condition may get better but it could
stay the same or even get worse. The information from this study might help in
the development of additional treatments for Small Cell Lung Cancer.
[Information on the risks associated with the study participation can be found
in Q E9 of this form]
Minervum 7061 Minervum 7061
Breda 4800DH
NL
Minervum 7061 Minervum 7061
Breda 4800DH
NL
Listed location countries
Age
Inclusion criteria
Subject has provided informed consent prior to initiation of any study-specific
activities/procedures • Age > 18 years old at the time of signing the
informed consent • Histologically or cytologically confirmed SCLC: o Parts A,
C, D, E, F and Part G: RR SCLC who progressed or recurred following at least 1
platinum-based regimen; Note: Subjects with a diagnosis of combined small cell
carcinoma with predominant small cells (as determined by the local pathologist)
may be considered for inclusion in the dose escalation phase of part A based on
investigator discretion and after discussion with the medical monitor o Part B:
ED SCLC with ongoing clinical benefit (stable disease [SD], partial response
[PR], or complete response [CR]) following no more than 6 cycles of first-line
platinum-based chemotherapy with the last dose of chemotherapy greater then
equal to 28 days prior to the study day 1 (first-line consolidation setting).
Part B will not be opened. • Eastern Cooperative Oncology Group (ECOG)
performance status of 0-2 • Minimum life expectancy of 12 weeks • RR SCLC only:
at least 2 measurable lesions as defined per modified RECIST 1.1 within 21 days
prior to the first dose of Tarlatamab. Subjects with 1 measurable lesion may be
considered for inclusion after discussion with the Medical Monitor. • Subjects
with treated brain metastases are eligible provided they meet the following
criteria: o Definitive therapy was completed at least 2 weeks prior to the
first dose of Tarlatamab. o There is no evidence of radiographic CNS
progression following definitive therapy and by the time of study screening.
Patients manifesting progression in lesions previously treated with
stereotactic radiosurgery may still be eligible if pseudo progression can be
demonstrated by appropriate means and after discussion with the medical
monitor. o Any CNS disease is asymptomatic for at least 7 days (unless symptoms
are deemed irreversible by the investigator), the patient is off steroids for
at least 7 days (physiologic doses of steroids are permitted), and the subject
is off or on stable doses of anti-epileptic drugs for malignant CNS disease for
at least 7 days. Please refer to section 4.1 of the protocol.
Exclusion criteria
History of other malignancy within the past 2 years prior to first dose of
Tarlatamab except: o Malignancy (other than in situ) treated with curative
intent and with no known active disease present for > 2 years before first
dose of Tarlatamab and felt to be at low risk for recurrence by the treating
physician. o Adequately treated non-melanoma skin cancer or lentigo maligna
without evidence of disease. o Adequately treated in situ cancer without
evidence of disease. o Prostatic intraepithelial neoplasia without evidence of
prostate cancer o Adequately treated urothelial papillary noninvasive carcinoma
• Major surgery within 28 days of first dose Tarlatamab • Untreated (includes
new lesions or progression in previously treated lesions) or symptomatic brain
metastases and leptomeningeal disease • Myocardial infarction and/or
symptomatic congestive heart failure (New York Heart Association > class II)
within 12 months of first dose of Tarlatamab • History of arterial thrombosis
(eg, stroke or transient ischemic attack) within 12 months of first dose of
Tarlatamab • Subject with symptoms and/or clinical signs and/or radiographic
signs that indicate an acute and/or uncontrolled active systemic infection
within 7 days prior to the first dose of investigational product administration
• Prior anti-cancer therapy: at least 28 days must have elapsed between any
prior anti-cancer therapy and first dose of Tarlatamab
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 | CTIS2023-506541-39-00 |
| EudraCT | EUCTR2017-003421-15-NL |
| ClinicalTrials.gov | NCT03319940 |
| CCMO | NL66035.031.18 |