1.
ClinicalTrials.gov; 13/02/2024; TrialID: NCT06268860
Clinical Trial Register
| ICTRP | ID: ictrp-NCT06268860
RESUMO
Condition:
Atopic DermatitisIntervention:
Drug: Rocatinlimab vial injection;Combination Product: Rocatinlimab prefilled syringePrimary outcome:
Maximum Observed Serum Concentration (Cmax) of Rocatinlimab;Area Under the Serum Concentration-time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Rocatinlimab;AUC From Time Zero to Infinity (AUCinf) of RocatinlimabCriteria:
Inclusion Criteria
1. Participant has provided informed consent before initiation of any study-specific
activities/procedures.
2. Healthy male or female participants, between 18 and 65 years of age (inclusive)
3. Body mass index between 18 and 32 kg/m^2 (inclusive)
Exclusion Criteria
1. History or evidence, at Screening or Check-in, of clinically significant disorder,
condition, or disease not otherwise excluded that, in the opinion of the Investigator
(or designee), would pose a risk to participant safety or interfere with the study
evaluation, procedures, or completion.
2. History or evidence of clinically significant arrhythmia at Screening, including any
clinically significant findings on the electrocardiogram (ECG) taken at Check-in.
3. A QT interval corrected for heart rate using Fridericia's method (QTcF) > 450 msec in
male participants or > 470 msec in female participants or history/evidence of long QT
syndrome at Screening or Check-in.
4. Systolic blood pressure > 140 mmHg or < 90 mmHg, or diastolic blood pressure > 90
mmHg, or pulse rate > 100 bpm
5. History of hypersensitivity, intolerance, or allergy to any drug compound, food, or
other substance, unless approved by the Investigator (or designee). Participants with
seasonal allergies will be permitted.
6. Estimated glomerular filtration rate less than 70 mL/min/1.73 m^2
7. Alanine aminotransferase or aspartate aminotransferase > 1.5 times the upper limit of
normal at Screening or Check-in.
8. Positive hepatitis B or hepatitis C panel (including positive hepatitis B surface
antigen [HBsAg] and/or positive hepatitis C antibody) and/or positive human
immunodeficiency virus test at Screening. Participants whose results are compatible
with prior hepatitis B vaccination (positive hepatitis B surface antibody, negative
hepatitis B core antibody, negative HBsAg) or prior infection (positive hepatitis B
core antibody, positive hepatitis B surface antibody, negative HBsAg) may be included.
9. Participants who have received live vaccines within 5 weeks prior to Screening, or
plan to receive live vaccines within 90 days after administration of an
investigational product.
Inactive vaccination (e.g., non-live or nonreplicating agent), including
coronavirus-2019 (COVID-19) vaccination, is allowed.
10. History of latent tuberculosis or active chronic, recurrent, or acute infection
requiring treatment with systemic antibiotics, antiviral, antiparasitic,
antiprotozoal, or antifungals which has not completely resolved, or for which therapy
has not been completed, within 4 weeks before Screening.
11. Use of any over-the-counter or prescription medications within 30 days or 5 half-lives
(whichever is longer) before Check-in, excluding the following:
1. Acetaminophen (paracetamol) (up to 2 g per day) for analgesia will be allowed.
2. Hormonal contraception listed in Appendix 3 will be allowed.
3. Hormone replacement therapy (e.g., estrogen) and hormonal contraceptives will be
allowed.
12. All herbal medicines (e.g., St. John's wort), vitamins, and supplements consumed by
the participant within the 30 days prior to Check-in, unless deemed acceptable by the
Investigator (or designee) and in consultation with the Sponsor.
13. Participant has received a dose of an investigational drug within the past 90 days or
5 half-lives, whichever is longer, prior to Check-in.
14. Have previously completed or withdrawn from this study or any other study
investigating rocatinlimab or have previously received rocatinlimab.
2.
ClinicalTrials.gov; 11/04/2022; TrialID: NCT05368103
Clinical Trial Register
| ICTRP | ID: ictrp-NCT05368103
RESUMO
Condition:
Alopecia AreataIntervention:
Biological: DaxdilimabPrimary outcome:
Percent change from baseline in Severity of Alopecia Tool (SALT) score at Week 24.Criteria:
Inclusion Criteria:
1. Willing and able to give informed consent.
2. Willing and able to comply with the prescribed treatment protocol and evaluations for
the duration of the trial.
3. Adult men or women 18 to 65 years of age.
4. Willing to keep the same hair style and color (eg, hair products, process, and timing
for hair appointments) for the duration of the trial.
5. Clinical diagnosis of moderate-to-severe AA - defined as meeting the following
criteria:
- Presence of = 50% and = 95% total scalp hair loss at screening and baseline (Day
1) defined by the SALT score.
- Duration of current episode of hair loss >3 months but <7 years at screening and
Day 1, along with investigators' assessment that hair regrowth is possible.
- No evidence of active regrowth present at baseline and no known history of
significant regrowth, as per investigator's judgement, over the last 6 months.
Exclusion Criteria:
1. Individuals involved in the conduct of the trial, their employees, or immediate family
members of such individuals.
2. Any clinically significant medical condition or physical/laboratory/ECG/vital signs
abnormality that would, in the opinion of the investigator, put the participant at
undue risk or interfere with the evaluation of the IP or interpretation of trial
results.
3. History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the
IP or to a previous monoclonal antibody (mAb) or human immunoglobulin (Ig) therapy.
4. Participant has had excessive sun exposure, is planning a trip to a sunny climate, or
has used tanning booths within 4 weeks prior to Day 1 or is not willing to minimize
natural and artificial sunlight exposure during the trial. Use of sunscreen products
and protective apparel are recommended when sun exposure cannot be avoided.
5. Known history of a primary immunodeficiency or an underlying condition such as known
human immunodeficiency virus (HIV) infection, a positive result for HIV infection,
splenectomy, or any underlying condition that in the opinion of the investigator
significantly predisposes the participant to infection.
6. Confirmed positive test for hepatitis B serology defined as:
- Hepatitis B surface antigen (HBsAg), or
- Hepatitis B core antibody (HBcAb or anti-HBc)
7. Positive test for hepatitis C virus antibody.
8. Active tuberculosis (TB), or a positive TB test at Screening. Participant will be
evaluated for latent TB infection with a purified protein derivative (PPD) test or a
QuantiFERON-TB Gold test. Participants who demonstrate evidence of latent TB infection
(either PPD =5 mm of induration or positive QuantiFERON-TB Gold test, irrespective of
bacille Calmette-Guérin vaccination status will not be allowed to participate in the
trial, unless documented history of appropriate treatment for active or latent TB.
Participants with an indeterminate test result can repeat the test, but if the repeat
test is also indeterminate, they are excluded.
9. Any severe herpes virus family infection (including Epstein-Barr virus,
cytomegalovirus [CMV]) at any time prior to Day 1, including, but not limited to,
disseminated herpes, herpes encephalitis, recent recurrent herpes zoster (defined as 2
episodes within the last 2 years), or ophthalmic herpes.
10. Any herpes zoster, CMV, or Epstein-Barr virus infection that was not completely
resolved 12 weeks prior to Day 1.
11. Any of the following within 30 days prior to signing the ICF and though Day 1:
- Clinically significant active infection in the opinion of the investigator,
including ongoing, and chronic infection requiring antibiotics or antiviral
medication (chronic nail infections are allowed). Note: Participant with a
limited recurrence of a cold sore or herpes genitalis between ICF signature and
Day 1 could be eligible based on the investigator's judgement.
- Any infection requiring hospitalization or treatment with intravenous (IV)
anti-infectives.
- A participant with a documented positive severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) test may be rescreened at least 2 weeks after a
positive test if the participant is asymptomatic and at least 3 weeks after
resolution of symptomatic Coronavirus Disease 2019 (COVID-19) illness.
12. Opportunistic infection requiring hospitalization or parenteral antimicrobial
treatment within 2 years prior to Day 1.
13. Any acute illness or evidence of clinically significant active infection, such as
fever = 38.0°C (= 100.5°F) on Day 1.
14. History of clinically significant cardiac disease including unstable angina;
myocardial infarction within 6 months prior to Day 1; congestive heart failure;
arrhythmia requiring active therapy, except for clinically insignificant extra
systoles, or minor conduction abnormalities; or presence of clinically significant
abnormality on ECG if, in the opinion of the investigator, it would increase the risk
of trial participation.
15. History of cancer or lymphoproliferative disease within 5 years prior to Day 1, except
as follows:
- In situ carcinoma of the cervix treated with apparent success with curative
therapy > 12 months prior to Screening, or
- Nonmetastatic cutaneous basal cell or squamous cell carcinoma of the skin treated
with apparent success with curative therapy.
16. Active forms of other inflammatory skin disease(s) or evidence of other skin
conditions (eg, psoriasis, seborrheic dermatitis, lupus) at the time of the Screening
and through Day 1, that in the opinion of the investigator might interfere with
evaluation of AA and the assessment of the activity measures.
17. Presence of another form of alopecia (except for androgenic alopecia).
18. History of male or female pattern hair loss > Hamilton stage III or > Ludwig stage II.
19. History or presence of hair transplants.
20. History or presence of micropigmentation of the scalp (Note: microblading of the
eyebrows is permitted).
21. Use of steroids (systemic and intralesional), anthralin, squaric acid,
diphenylcycloprophenone (DPCP), dinitrochlorobenzene (DCNB), protopic, minoxidil, or
any other medication which in the opinion of the investigator may affect hair regrowth
within 4 weeks of Day 1 visit. Note: Intranasal and inhaled corticosteroids are
allowed, eye and ear drops containing corticoster
3.
ClinicalTrials.gov; 17/09/2021; TrialID: NCT05060016
Clinical Trial Register
| ICTRP | ID: ictrp-NCT05060016
RESUMO
Condition:
Relapsed/Refractory Small Cell Lung CancerIntervention:
Drug: TarlatamabPrimary outcome:
Part 1 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator;Part 1 and Part 3 Only: Number of Participants who Experience One or More Treatment-emergent Adverse Events;Part 1 Only: Serum Concentrations of Tarlatamab;Part 1 and Part 2 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)Criteria:
Inclusion Criteria:
- Participant has provided informed consent/assent prior to initiation of any study
specific activities/procedures.
- Male and female participants = 18 years of age (or legal adult age within country) at
the time of signing the informed consent.
- Histologically or cytologically confirmed relapsed/refractory SCLC
- Participants who progressed or recurred following 1 platinum-based regimen and at
least 1 other prior line of therapy.
- Participants willing to provide archived tumor tissue samples or willing to undergo
pretreatment tumor biopsy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 1.
- Minimum life expectancy of 12 weeks.
- Measurable lesions as defined per RECIST 1.1 within 21 days prior to the first dose of
tarlatamab.
- Participants with treated brain metastases are eligible provided they meet defined
criteria.
Exclusion Criteria:
Disease Related
- Untreated or symptomatic brain metastases and leptomeningeal disease.
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Participants who experienced recurrent pneumonitis (grade 2 or higher) or severe,
life-threatening immune-mediated adverse events or infusion-related reactions
including those that lead to permanent discontinuation while on treatment with
immuno-oncology agents.
- Unresolved toxicity from prior anti-tumor therapy, defined as per protocol.
Other Medical Conditions
- History of other malignancy within the past 2 years, with exceptions
- 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.
- Participant 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 tarlatamab.
- Presence of any indwelling line or drain.
- History of hypophysitis or pituitary dysfunction.
- Exclusion of hepatitis infection based on the results and/or criteria per protocol.
- Major surgery within 28 days of first dose of tarlatamab.
- History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection. Subject is eligible if no acute symptoms of coronavirus disease 2019
(COVID-19) within 14 days prior to first dose of tarlatamab (counted from day of
positive test for asymptomatic subjects).
Prior/Concomitant Therapy
- Participant received prior therapy with tarlatamab.
- Prior anti-cancer therapy within 28 days prior to first dose of tarlatamab.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of
tarlatamab.
- The following vaccines (live and live-attenuated vaccines) are excluded during the
following study periods:
1. Screening and during study treatment: Live and live-attenuated vaccines are
prohibited within 28 days prior to the first dose of tarlatamab and for the
duration of the study. Live viral non-replicating vaccine (e.g. Jynneos) for
Monkeypox infection is allowed during the study (except during cycle 1) in
accordance with local standard of care and institutional guidelines.
2. End of study treatment: Live and live-attenuated vaccines can be used when at
least 42 days (5X half-life of tarlatamab) have passed after the last dose of
tarlatamab.
Other Exclusions
- Female participants of childbearing potential unwilling to use protocol specified
method of contraception during treatment and for an additional 72 days after the last
dose of tarlatamab.
- Female participants who are breastfeeding or who plan to breastfeed while on study
through 72 days after the last dose of tarlatamab.
- Female participants planning to become pregnant while on study through 72 days after
the last dose of tarlatamab.
- Female participants of childbearing potential with a positive pregnancy test assessed
at screening and/or day 1 by a highly sensitive urine or serum pregnancy test.
- Male participants with a female partner of childbearing potential who are unwilling to
practice sexual abstinence (refrain from heterosexual intercourse) or use
contraception during treatment and for an additional 132 days after the last dose of
tarlatamab.
- Male participants with a pregnant partner who are unwilling to practice abstinence or
use a condom during treatment and for an additional 132 days after the last dose of
tarlatamab.
- Male participants unwilling to abstain from donating sperm during treatment and for an
additional 132 days after the last dose of tarlatamab.
- Participant has known sensitivity to any of the products or components to be
administered during dosing.
- Participant likely to not be available to complete all protocol-required study visits
or procedures, and/or to comply with all required study procedures.
- History or evidence of any other clinically significant disorder, condition or disease
determined by the investigator or Amgen physician.
Specific Exclusions to Part 3
- Participants unable to remain within one hour of study site for 48 hours after
infusion of tarlatamab on Cycle 1 Day 1 and Cycle 1 Day 8.
- Participants unable to remain within one hour of any hospital for 72 hours after
infusion of tarlatamab on Cycle 1 Day 1 and Cycle 1 Day 8.
- Unable to identify home companion who will cohabitate with participant for 72 hours
after infusion of tarlatamab on Cycle 1 Day 1 and Cycle 1 Day 8.
4.
ClinicalTrials.gov; 02/08/2021; TrialID: NCT04998747
Clinical Trial Register
| ICTRP | ID: ictrp-NCT04998747
RESUMO
Condition:
Relapsed/Refractory Multiple MyelomaIntervention:
Drug: AMG 701;Drug: AMG 701Primary outcome:
Number of participants who experience dose-limiting toxicities (DLTs);Number of participants who experience one or more treatment-emergent adverse events (TEAEs);Number of participants who experience one or more treatment-related TEAEs;Number of participants with abnormal changes in vital signs;Number of participants with abnormal changes in electrocardiograms (ECGs) findings;Number of participants with abnormal changes in clinical laboratory testsCriteria:
Inclusion Criteria:
- Participant has provided informed consent prior to initiation of any study specific
activities/procedures.
- Age 18 years or older at the time of signing the informed consent.
- Relapsed or relapsed and refractory multiple myeloma according to International
Myeloma Working Group (IMWG) criteria.
- Participants must have received = 3 prior therapies that must include all approved and
available therapies deemed eligible by the investigator, including at a minimum, a
proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and a CD38-directed
antibody. Note: Participants may have received prior treatment targeting BCMA that is
not AMG 701.
- Participants must have measurable disease, defined by 1 or more of the following at
time of screening :
- A serum M protein = 0.5 g/dL measured by serum protein electrophoresis (SPEP)
- Urinary M protein excretion = 200 mg/24 hours
- Involved serum free light chain (sFLC) measurement = 10 mg/dL, provided that SFLC
ratio is abnormal as per IMWG response criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2.
- Life expectancy of at least 3 months as per investigator's judgment at time of
screening
- Hematological function without transfusion support as follows:
- Absolute neutrophil count = 1.0 x 10^9/L (without growth factor support)
- Platelet count = 50 x 10^9/L (without transfusions within 7 days from screening
assessment)
- Hemoglobin = 8.0 g/dL (transfusions permitted no later than 48 hours before
screening)
- Renal function as follows:
Calculated or measured creatinine clearance = 30 mL/min using:
- The Cockcroft-Gault equation OR
- Via 24-hour urine collection with plasma and urine creatinine concentrations
- Hepatic function as follows:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x upper
limit of normal (ULN)
- Total bilirubin (TBIL) < 1.5 x ULN (unless considered due to Gilbert's syndrome)
- Cardiac function as follows:
- Left ventricular ejection fraction = 50% as assessed by transthoracic echocardiogram
(TTE) or multigated acquisition (MUGA) scan.
- Serum sodium, potassium, phosphorus, calcium, and magnesium must be within normal
range or if outside normal range must have resolved to Common Terminology
Criteria for Adverse Events (CTCAE) version 5.0 grade 1 within 7 days of day 1.
Participants not meeting these inclusion criteria may be treated with replacement
therapy and re-screened up to 2 times at the discretion of the investigator.
- Participants with prior COVID-19 infection or history of cardiovascular disease
including coronary artery disease, significant valvular disease, cardiac
arrhythmia, cardiomyopathy, or history of cardiac toxicity with prior therapy
must have a cardiology consultation during screening with a clinical management
plan during cytokine release syndrome (CRS) prior to cycle 1 day 1 therapy.
- Participants with a history of COVID-19 infection must be discussed with the
medical monitor prior to enrollment. Participants with a history of COVID-19
infection must have a negative quantitative polymerase chain reaction (PCR) test
prior to enrollment.
Exclusion Criteria:
- Known central nervous system involvement by multiple myeloma.
- Recent history of primary plasma cell leukemia (within last 6 months prior to
enrollment) or evidence of primary or secondary plasma cell leukemia at the time of
screening.
- Waldenström macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, skin changes), or amyloidosis (participants with
multiple myeloma with asymptomatic amyloid plaques found on biopsy would be eligible
if all other criteria are met).
- History or evidence of any of the following cardiovascular disorders:
- Active congestive heart failure (New York Heart Association Class III to IV)
- Symptomatic ischemia
- Uncontrolled arrhythmias
- Screening ECG with corrected QT interval (QTc) of > 470 msec
- Myocardial infarction within 12 months prior to study day 1
- History of malignancy other than multiple myeloma within the past 3 years with the
following exceptions:
- Malignancy treated with curative intent and with no known active disease present
for at least 1 year before enrollment and felt to be at low risk for recurrence
by the treating physician.
- Adequately treated cervical carcinoma in situ without evidence of disease.
- Breast ductal carcinoma in situ with full surgical resection (ie, negative
margins) and without evidence of disease
- Prostate cancer with a Gleason score < 7 with undetectable prostate specific
antigen over 12 months
- Treated medullary or papillary thyroid cancer
- Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
situ
- Similar neoplastic conditions with an expectation of > 95% 5-year disease-free
survival
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.
- Clinically uncontrolled chronic or ongoing bacterial, fungal, viral, or other
infectious disease at study day 1 or within 14 days before study day 1.
- Positive result for human immunodeficiency virus (HIV).
- Active hepatitis B and C based on the following results:
- Positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic
hepatitis B or recent acute hepatitis B)
- Negative HepBsAg and positive for hepatitis B core antibody: Either a positive
hepatitis B surface antibody or a negative hepatitis B virus DNA by PCR result is
necessary for enrollment
- Positive hepatitis C virus antibody: Negative hepatitis C virus RNA by PCR result
is necessary for enrollment
- Unresolved toxicities from prior anticancer therapy, defined as not having resolved to
CTCAE version 5.0 grade 1 or to levels dictated in the eligibility criteria with the
exception of grade 2 peripheral neuropathy, alopecia or toxicities from prior
anticancer therapy that are considered irreversible (defined
5.
ClinicalTrials.gov; 05/04/2021; TrialID: NCT04833855
Clinical Trial Register
| ICTRP | ID: ictrp-NCT04833855
RESUMO
Condition:
Chronic Spontaneous UrticariaIntervention:
Biological: Tezepelumab Dose 1;Biological: Tezepelumab Dose 2;Biological: Omalizumab;Biological: PlaceboPrimary outcome:
Change from Baseline in Urticaria Activity Score over 7 days (UAS7)Criteria:
Inclusion Criteria:
- Signed informed consent must be obtained prior to participation in the study.
- Male and female participants = 18 years and = 80 years of age at the time of
screening.
- Chronic spontaneous urticaria (CSU) diagnosis for = 6 months at the time of screening.
- CSU inadequately controlled by second generation H1-antihistamines (sgAH) at
enrollment, as defined by all of the following:
- The presence of itch and hives for >= 6 consecutive weeks at any time prior to
screening visit 2
- Failure to respond to an sgAH (up to 4 times the approved dose)
- Urticaria Activity Score over 7 days (UAS7) (range 0-42) >= 16 and Hives Severity
Score over 7 days (HSS7) (range 0-21) >= 8 during the 7 days prior to enrollment
- Participant with CSU who discontinued, is intolerant to, or was an inadequate
responder to anti-IgE therapies despite being treated with omalizumab 300 mg every 4
weeks (Q4W) for 6 months or higher doses of omalizumab > 2 months or another anti-IgE
therapy. Note: This criterion is only applicable for anti-IgE-experienced
participants.
- Participant willing and able to complete a daily symptom eDiary for the duration of
the study and adhere to the study visit schedules.
- Subject must have been on a sgAH at approved or increased doses (up to 4x the approved
dose) for treatment of CSU for at least 3 consecutive days immediately prior to the
day -14 screening visit (screening visit 2) and must have documented current use on
the day of screening visit 1
Exclusion Criteria:
Disease related, including but not limited to:
- Urticaria is solely due to inducible urticaria
- Active dermatologic diseases (or conditions) other than chronic urticaria, with
urticaria wheals or angioedema symptoms such as urticarial vasculitis, erythema
multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired
angioedema (eg, due to C1 inhibitor deficiency)
- Any other active skin disease associated with chronic itching that might influence, in
the investigator's opinion, the study evaluations and results (eg, atopic dermatitis,
dermatitis herpetiformis, senile pruritus, etc.)
- History of a clinically significant infection within 28 days prior to day 1 that, in
the opinion of the investigator or medical monitor, might compromise the safety of the
participant in the study, interfere with evaluation of the investigational product, or
reduce the participants ability to participate in the study.
- Evidence of active tuberculosis (TB) (in the opinion of the investigator), either
treated or untreated, or a positive purified protein derivative (PPD) or
QuantiFERON-TB Gold Plus (QFT-Plus) test for TB during screening.
- History of malignancy, except for basal cell carcinoma or in situ carcinoma of the
cervix treated with apparent success with curative therapy = 12 months prior to
screening or other malignancies treated with apparent success with curative therapy =
5 years prior to screening visit 1.
- Subject is unable to complete an electronic patient diary or complete questionnaires,
or does not meet the required level of compliance with the eDiary during the 14 days
sgAH stabilization period
Other medical conditions
- History or evidence of severe depression, schizophrenia, previous suicide attempts, or
suicidal ideation.
Prior/concomitant therapy, including but not limited to:
- Treatment with any biologic products (eg, omalizumab, ligelizumab) within 4 months or
5 half-lives (whichever is longer) prior to screening visit 1
- Routine (daily or every other day for 5 or more consecutive days) use of systemic
corticosteroids, systemic hydroxychloroquine, methotrexate, cyclosporine A,
cyclophosphamide, tacrolimus, azathioprine, and mycophenolate mofetil within 30 days
prior to screening visit 1.
- Major surgery within 8 weeks prior to screening visit 1 or planned inpatient surgery
or hospitalization during the study period.
- Receipt of Ig or blood products within 30 days prior to screening visit 1.
- Vaccination with a live or attenuated vaccine within 30 days prior to screening visit
1. Receipt of COVID-19 vaccines and inactive/killed vaccinations (eg, inactive
influenza) are allowed, provided the vaccinations are not administered within 7 days
before or after any study dosing visit.
- Known hypersensitivity, including severe hypersensitivity reactions and/or history of
anaphylactic shock, to any of the products or components to be administered during
dosing or to products of similar chemical classes (ie, to murine, chimeric, or human
antibodies.
6.
ClinicalTrials.gov; 07/01/2021; TrialID: NCT04702737
Clinical Trial Register
| ICTRP | ID: ictrp-NCT04702737
RESUMO
Condition:
Neuroendocrine Prostate CancerIntervention:
Drug: TarlatamabPrimary outcome:
Number of Participants who Experience One or More Treatment-emergent Adverse Events (TEAEs);Number of Participants who Experience One or More Treatment-related Adverse Events;Number of Participants who Experience a Clinically Significant Change from Baseline in Vital Signs;Number of Participants who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements;Number of Participants who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests;Number of Participants who Experience Dose Limiting Toxicities (DLTs)Criteria:
Inclusion Criteria (Part 1: Dose Exploration and Part 2: Dose Expansion):
- Participant has provided informed consent prior to initiation of any study specific
activities/procedures.
- Men aged = 18 years at time of signing the informed consent.
- Metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC) defined
by histology, immunohistochemistry, or genomic analyses of baseline tumor tissue (by
local assessment) or circulating tumor DNA (ctDNA) (by local assessment) as per
protocol
- At least 1 line of prior systemic treatment per protocol.
- Participants with treatment-emergent NEPC or de novo NEPC with histologic evidence of
prostate cancer with neuroendocrine differentiation without a history of bilateral
orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH)
analogue therapy during the course of protocol therapy
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per
Prostate Cancer Working Group 3 (PCWG3) modifications
- Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2
- Participants with treated brain metastases are eligible provided they meet defined
criteria
- Adequate organ function as defined in protocol
Exclusion Criteria (Part 1: Dose Exploration and Part 2: Dose Expansion):
- History of other malignancy within the past 2 years, with exceptions:
- Malignancy treated with curative intent and with no known active disease present
for = 2 years before enrollment and felt to be at low risk for recurrence by the
treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
- Adequately treated non-muscle invasive urothelial carcinoma
- History or presence of hematological malignancies unless curatively treated with no
evidence of disease = 2 years
- Untreated or symptomatic brain metastases and leptomeningeal disease
- Anti-tumor therapy within 28 days of study day 1; concurrent use of hormone
deprivation therapy for hormone refractory prostate cancer is permitted; participants
on a stable bisphosphonate or denosumab prior to study day 1 are eligible
Exceptions:
- Participants who received conventional chemotherapy are eligible if at least 14 days
have elapsed and if all treatment-related toxicities have resolved to Grade = 1
- Prior palliative radiotherapy must have been completed at least 7 days before the
first dose of tarlatamab
- Participants who received androgen signaling inhibitor are eligible if at least 14
days have elapsed and if all treatment-related toxicity has been resolved to Grade = 1
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or
any other form of immunosuppressive therapy within 7 days prior study day 1
- Active autoimmune disease requiring systemic treatment within the past 2 years
- Known positive test for human immunodeficiency virus (HIV) or hepatitis
- Unresolved toxicities from prior anti-tumor therapy, defined as not having
resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
grade 0 or 1 (with the exception of alopecia or toxicities that are stable and
well-controlled)
- History of hypophysitis or pituitary dysfunction
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Participants on prior delta-like ligand 3 (DLL3)-targeted therapy may be eligible
if discussed with Amgen Medical Monitor prior to enrollment
- Evidence of severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection
unless agreed upon with Medical Monitor and with no acute symptoms of coronavirus
disease 2019 (COVID19) disease within 14 days prior to first dose of
investigational product (counted from day of positive test for asymptomatic
participants).
7.
ClinicalTrials.gov; 14/10/2020; TrialID: NCT04590586
Clinical Trial Register
| ICTRP | ID: ictrp-NCT04590586
8.
EU Clinical Trials Register; 17/07/2020; TrialID: EUCTR2020-001305-23-DE
Clinical Trial Register
| ICTRP | ID: ictrp-EUCTR2020-001305-23-DE
RESUMO
Condition:
Metastatic Castration-resistant Prostate CancerMedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 100000004864 ;Therapeutic area: Diseases [C] - Cancer [C04]
Intervention:
Product Name: AMG 160
Product Code: AMG 160
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: Pending
Current Sponsor code: AMG 160
Other descriptive name: AMG 160
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.28-
Product Name: AMG 404
Product Code: AMG 404
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pending
Current Sponsor code: AMG 404
Other descriptive name: AMG 404
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 70-
Primary outcome:
Main Objective: All subprotocolsTo evaluate the safety, tolerability, and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of investigational therapies in subjects with metastatic castration-resistant prostate cancer (mCRPC)
Subprotocol C Part 3 only
•To evaluate preliminary anti-tumor activity of AMG 404 monotherapy;Secondary Objective: All subprotocols
•To evaluate preliminary anti-tumor activity of investigational therapies in subjects with mCRPC
•To characterize the pharmacokinetics (PK) of investigational therapies in subjects with mCRPC
Subprotocol C part 3 only
• Safety: To evaluate the safety and tolerability of AMG 404 monotherapy
• Efficacy: To evaluate anti-tumor activity of AMG 404 monotherapy with additional measures;Primary end point(s): All subprotocols
• dose-limiting toxicities (DLTs)
• treatment-emergent and treatment-related adverse events
• changes in vital signs, and clinical laboratory tests
Subprotocol C Part 3
• objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications
• circulating tumor cell (CTC) response (CTC0 and CTC conversion)
• prostate-specific antigen (PSA) response;Timepoint(s) of evaluation of this end point: The analysis of all endpoints, unless noted otherwise, will be conducted on the Safety Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of AMG 160 (or AMG 404 in Parts 1 and 2 and at least 1 dose of AMG 404 in Part 3 - Subprotocol C).
Criteria:
Inclusion criteria:All Subprotocols
- Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate without pure neuroendocrine differentiation or small cell features
- Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist.
- Total serum testosterone should be = 50 ng/dL (or 1.7 nmol/L)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 1
- Life expectancy of > 3 months
- Adequate organ function, defined as follows:
• absolute neutrophil count = 1.5 x 10^9/L (without growth factor support within 7 days from screening assessment)
• platelet count = 100 x 10^9/L (without platelet transfusion within 7 days from screening assessment)
• hemoglobin > 9 g/dL (90 g/L) (subprotocol A & C) / > 10 g/dL (100g/L) (subprotocol B) (without blood transfusion within 7 days from screening assessment)
• estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation = 30 mL/min/1.73 m2
• AST and ALT < 3 x upper limit of normal (ULN) (or < 5 x ULN for subjects with liver involvement)
• total bilirubin (TBL) < 1.5 x ULN (or < 2 x ULN for subjects with liver metastases)
• left ventricular ejection fraction (LVEF)> 50% (2-D transthoracic echocardiogram [ECHO] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if ECHO is not available)
- Baseline electrocardiogram (ECG) QTc = 470 msec
Subprotocol A & B only
- Subjects planning to receive enzalutamide (subprotocol A) / abiraterone (subprotocol B) for the first time for mCRPC (subjects who received prior enzalutamide (subprotocol A) / abiraterone (subprotocol B) are not eligible).
Subprotocol C only
- Subjects who are refractory to a novel antiandrogen therapy (abiraterone, apalutamide, and/or enzalutamide) given for metastatic or non-metastatic prostate cancer. Subjects must be ineligible for or refuse taxane therapy.
- Evidence of progressive disease, defined as 1 or more PCWG3 criteria:
• PSA level of at least 1 ng/mL that has risen on at least 2 successive occasions at least 1 week apart
• nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications
• appearance of 2 or more new lesions in bone scan
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 65
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 64
Exclusion criteria:
All Subprotocols
- Pathological finding consistent with pure small cell, neuroendocrine carcinoma of the prostate or any other histology different from adenocarcinoma
- CNS metastases/leptomeningeal disease
- Symptomatic peripheral sensory/motor neuropathy =grade3
- History/presence of clinically relevant CNS pathology
- Confirmed history/current autoimmune disease or other diseases resulting in permanent immunosuppression/requiring permanent immunosuppressive therapy
- Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials (Subprotocol A&B) /active fungal, bacterial, viral, or other infection requiring systemic therapy (Subprotocol C) within 7days of dosing
- History/evidence of inflammatory bowel disease or any other GI disorder causing chronic nausea, vomiting, or diarrhea
- History of arterial/venous thrombosis within 12months of 1st dose
- Myocardial infarction, uncontrolled hypertension (Subprotocol A&C), unstable angina, cardiac arrhythmia requiring medication, &/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months (Subprotocol A&B) /within 6months (Subprotocol C) of 1st dose of AMG 160
- Unresolved toxicities from prior anti-tumor therapy not having resolved to CTCAE version 5.0 grade 1, except for alopecia or toxicities that are stable and well-controlled & there is agreement to allow by both the investigator & sponsor
- Known HIV infection, hepatitis C or hepatitis B infection
- History of other malignancy within the past 2years, with the following exceptions:
• Malignancy treated with curative intent & with no known active disease present for =3 years before enrollment and felt to be at low risk for recurrence by treating physician
• Adequately treated non-melanoma skin cancer/lentigo maligna without evidence of disease
• Adequately treated urothelial papillary noninvasive carcinoma/carcinoma in situ
- Prior treatment with a taxane for mCRPC
- Radiation therapy within 4weeks of 1st dose (or local or focal radiotherapy within 2 weeks)
- Any anticancer therapy/immunotherapy within 4 weeks (2 weeks Subprotocol C) of start of 1st dose, not including LHRH/GnRH analogue. Subjects on a stable bisphosphonate/denosumab regimen for =30 days prior to enrollment are eligible
- Prior PSMAxCD3 bispecific therapy (not subprotocol C part 3)
- Requiring chronic systemic corticosteroid therapy/any other immunosuppressive therapies. Low dose corticosteroids permitted
- Prior major surgery within 4 weeks of 1st dose
- Currently receiving treatment in another investigational device/drug study, or <4 weeks since ending treatment on another investigational device or drug study
- Male subjects with a female partner of childbearing potential/pregnant partner who are unwilling to practice sexual abstinence/use contraception during treatment and for an additional 4 months (Subprotocol A&B) /8 months (Subprotocol C) after the last dose
- Male subjects unwilling to abstain from donating sperm during treatment and for an additional 4 months (Subprotocol A&B) /8 months (Subprotocol C) after the last dose
- Subject has known sensitivity to any of the products (or components) to be administered during dosing
- Subject likely to not be available to complete all protocol-required study visits/procedures, &/or to comply with all required study procedures
- History/evidence of any other clinically significant disorder, condition or disease (except for those outlined above) that, in