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JOURNAL ONKOLOGIE – STUDIE

Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)

Rekrutierend

NCT-Nummer:
NCT05489211

Studienbeginn:
September 2022

Letztes Update:
09.08.2024

Wirkstoff:
Datopotamab deruxtecan (Dato-DXd), Capecitabin, 5-Fluorouracil, Volrustomig, Carboplatin, Leucovorin LV, Bevacizumab, Rilvegostomig, Prednisone/ prednisolone, Cisplatin

Indikation (Clinical Trials):
Endometrial Neoplasms, Biliary Tract Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
AstraZeneca

Collaborator:
Daiichi Sankyo

Studienleiter

Global Clinical Lead, MD
Principal Investigator
AstraZeneca

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com» Kontaktdaten anzeigen

Studienlocations
(3 von 94)

Research Site
45136 Essen
(Nordrhein-Westfalen)
GermanyZurückgezogen» Google-Maps
Research Site
30625 Hannover
(Niedersachsen)
GermanyZurückgezogen» Google-Maps
Research Site
90095 Los Angeles
United StatesNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This Phase II, open-label, uncontrolled, multicentre study evaluating the efficacy and

safety of Dato-DXd as monotherapy (MONO) and in combination with anticancer agents

(COMBO) in various advanced solid tumour types.

This study has a modular design, as such a master protocol with independent substudies

enables simultaneous evaluation of the safety profile, recommended Phase II dose (RP2D),

and efficacy of Dato-DXd in multiple disease populations and treatment combinations. This

study will evaluate various solid tumour types, including endometrial cancer (Substudy

1), gastric cancer (Substudy 2), metastatic castration-resistant prostate cancer (mCRPC)

(Substudy 3), ovarian cancer (Substudy 4), colorectal cancer (CRC) (Substudy 5),

urothelial cancer (Substudy 6), and biliary tract cancer (Substudy 7) in the advanced or

metastatic setting. Within each substudy, Dato-DXd will be evaluated as monotherapy (for

all substudies except Substudy 2) and in combination with approved or novel anticancer

agents that may be active in the tumour type being evaluated (for all substudies except

Substudy 1 and Substudy 7).

Ein-/Ausschlusskriterien

Key Inclusion Criteria:

- Male and female, ≥ 18 years

- Documented advanced or metastatic malignancy

- Eastern Cooperative Oncology Group performance status of 0 or 1 with no

deterioration over the 2 weeks prior to baseline or day of first dosing

- All participants must provide a tumour sample for tissue-based analysis

- At least 1 measurable lesion not previously irradiated, except Substudy 3 (Prostate

Cancer) which allows participants with non measurable bone metastatic disease

- Adequate bone marrow reserve and organ function

- Minimum life expectancy of 12 weeks

- At the time of screening, contraceptive use by men or women should be consistent

with local regulations regarding the methods of contraception for those

participating in clinical studies

- All women of childbearing potential must have a negative serum pregnancy test

documented during screening

- Female participants must be 1 year post-menopausal, surgically sterile, or using 1

highly effective form of birth control. Female participants must not donate, or

retrieve for their own use, ova at any time during this study

- Male participants who intend to be sexually active with a female partner of

childbearing potential must be surgically sterile, avoid intercourse, or use a

highly effective method of contraception. Male participants must not freeze or

donate sperm at any time during this study.

- Capable of giving signed informed consent

- Provision of signed and dated written optional genetic research informed consent

prior to collection of samples for optional genetic research that supports the

Genomic Initiative

Key Exclusion Criteria:

- Any evidence of diseases which, in the investigator's opinion, makes it undesirable

for the participant to participate in the study or that would jeopardize compliance

with the protocol

- History of another primary malignancy except for adequately resected basal cell

carcinoma or in situ squamous cell carcinoma of the skin, or other solid malignancy

treated with curative intent

- Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not

yet improved

- Irreversible toxicity that is not reasonably expected to be exacerbated by study

intervention in the opinion of the investigator, for example hearing loss

- Spinal cord compression or brain metastases unless treated

- Leptomeningeal carcinomatosis

- Clinically significant corneal disease

- Active hepatitis or uncontrolled hepatitis B or C virus infection

- Uncontrolled infection requiring IV antibiotics, antivirals or antifungals, for

example prodromal symptoms

- Known HIV infection that is not well controlled

- Known active tuberculosis infection

- Mean resting corrected QTcF > 470 ms

- In the judgement of the investigator, history of QT prolongation associated with

other medications that required discontinuation of that medication, or any current

concomitant medication known to prolong the QT interval and cause TdP

- In the judgement of the investigator, congenital long QT syndrome, family history of

long QT syndrome, or unexplained sudden death under 40 years of age in first-degree

relatives

- Uncontrolled or significant cardiac diseases

- History of non-infectious Interstitial lung disease (ILD)/pneumonitis that required

steroids

- Has severe pulmonary function compromise

- Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment

washout period

- Receipt of live, attenuated vaccine within 30 days prior to the first dose of study

intervention

- Prior exposure to anticancer therapies without an adequate treatment washout period

prior to enrolment or any concurrent anticancer treatment

- Palliative radiotherapy with a limited field of radiation within ≤ 2 weeks or to

more than 30% of the bone marrow within ≤ 4 weeks before the first dose of study

intervention

- Major surgical procedure or significant traumatic injury within ≤ 3 weeks of the

first dose of study intervention or an anticipated need for major surgery during the

study

- Prior treatment with TROP2-directed therapies or other antibody-drug conjugate

(ADCs) with deruxtecan payload

- Herbal or natural products intended as treatment or prophylaxis for any type of

cancer that may interfere with the activity of the study intervention

- Previous treatment in the present study

- Participation in another clinical study with a study intervention or investigational

medicinal device administered in the last 4 weeks prior to first dose of study

intervention or concurrent enrolment in another clinical study

- Severe hypersensitivity to Dato-DXd or any of the excipients, including but not

limited to polysorbate 80 or other monoclonal antibodies

- Involvement in the planning and/or conduct of the study

- Judgment by the investigator that the participant should not participate in the

study if the participant is unlikely to comply with study procedures, restrictions,

and requirements

- Females that are pregnant, breastfeeding, or planning to become pregnant

- Female participants should refrain from breastfeeding from enrolment throughout the

study and for at least 7 months after last dose of Dato-DXd

Studien-Rationale

Primary outcome:

1. Objective response rate (ORR) (Time Frame - From baseline to progressive disease or death (approximately 1 year)):
Proportion of participants who have a confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST 1.1.

2. The number of subjects with adverse events/serious adverse events (Time Frame - Throughout the treatment and the safety follow-up period 28 [+ 7] days after the discontinuation of all study interventions, except durvalumab, nivolumab, and bevacizumab for which it will be 90 [+ 7] days (approximately 1 year)):
Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal Electrocardiogram (ECG) parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline.

3. PSA50 response (Substudy 3 only) (Time Frame - From baseline to PSA response evaluated according to the PCWG3 criteria (up to 12 weeks)):
Proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later.

4. Progression free survival (PFS) response (Substudy 4C only) (Time Frame - From baseline to progressive disease or death (approximately 1 year)):
PFS is defined as time from start of treatment until progression per RECIST 1.1 as assessed by the investigator or death due to any cause.

Secondary outcome:

1. Progression free survival (PFS) (Time Frame - From baseline to progressive disease or death (approximately 1 year)):
PFS is defined as time from start of treatment until progression per RECIST 1.1 as assessed by the investigator or death due to any cause.

2. Duration Of Response (DoR) (Time Frame - From baseline to progressive disease or death (approximately 1 year)):
DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by the investigator or death.

3. Disease Control Rate (DCR) (Time Frame - At 12 and 14 weeks):
DCR at 12 and 24 weeks is defined as the percentage of participants who have a Complete response (CR) or Partial response (PR) in the first 13 and 25 weeks or who have Stable disease (SD) for at least 11 and 23 weeks after the date of first dose respectively, per RECIST 1.1 as assessed by the investigator at local site and derived from the raw tumour data.

4. Best percentage change in tumour size (Time Frame - From baseline to progressive disease or death (approximately 1 year)):
The best percentage change from baseline in tumour size will be derived as the maximum reduction from baseline or (in the absence of reduction) the minimum increase from baseline.

5. Pharmacokinetics of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): Maximum plasma concentration of the drug (Cmax) (Time Frame - At predefined intervals throughout the treatment period (approximately 1 year)):
The concentration in plasma will be determined.

6. Pharmacokinetics of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): The time taken to reach the maximum concentration (Tmax) (Time Frame - At predefined intervals throughout the treatment period (approximately 1 year)):
The concentration in plasma will be determined.

7. Pharmacokinetic Parameter of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): Area under the plasma concentration- time curve (AUC) (Time Frame - At predefined intervals throughout the treatment period (approximately 1 year)):
The concentration in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.

8. Plasma concentration of Total anti-TROP2 antibody (Time Frame - Throughout the treatment period at pre-defined intervals (approximately 1 year)):
Expression of TROP2 will be measured in blood sample

9. Plasma concentration of MAAA-1181a (Time Frame - Throughout the treatment period at pre-defined intervals (approximately 1 year)):
The concentration in plasma will be determined (Cmax will be derived).

10. Anti Drug Antibody (ADA) for Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6) (Time Frame - Throughout the treatment period at pre-defined intervals and including the safety follow-up period (approximately 1 year)):
Whole blood samples for determination of ADA in plasma will be collected; Percentage of patients who develop ADA

11. Radiographic PFS (Substudy 3) (Time Frame - From baseline to radiographic progression or death (approximately 1 year)):
PFS is defined as time from start of treatment until radiographic progression per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone) as assessed by the investigator or death.

12. PSA progression (Substudy 3) (Time Frame - From baseline to PSA response evaluated according to the PCWG3 criteria (up to 12 weeks)):
PSA progression is defined as an increase in PSA (after Week 12) of ≥25% greater than the nadir and an absolute increase of at least 2 ng/mL above nadir.

13. CA-125 response (Substudy 4) (Time Frame - From baseline to CA-125 response evaluated according to the GCIG criteria (up to 12 weeks)):
Proportion of participants achieving a > 50% reduction in CA-125 levels from a pre-treatment sample confirmed and maintained for at least 28 days.

14. Overall survival (OS) (Substudy 4) (Time Frame - From baseline to death (approximately 1 year)):
OS is defined as time from start of treatment until death.

Studien-Arme

  • Experimental: Substudy-1A
    Dato-DXd will be evaluated as monotherapy
  • Experimental: Substudy-2A
    Dato-DXd in combination with capecitabine will be evaluated
  • Experimental: Substudy-2B
    Dato-DXd in combination with 5-FU will be evaluated
  • Experimental: Substudy-3A
    Dato-DXd will be evaluated as monotherapy
  • Experimental: Substudy-3C
    Dato-DXd will be evaluated in combination with prednisone/prednisolone
  • Experimental: Substudy-4A
    Dato-DXd will be evaluated as monotherapy
  • Experimental: Substudy-4C
    Dato-DXd in combination with carboplatin + bevacizumab followed by Dato-DXd + bevacizumab will be evaluated
  • Experimental: Substudy-5A
    Dato-DXd will be evaluated as monotherapy
  • Experimental: Substudy-5B
    Dato-DXd + 5-FU + LV + bevacizumab OR Dato-DXd + capecitabine + bevacizumab will be evaluated
  • Experimental: Substudy-6A
    Dato-DXd in combination with volrustomig (MEDI5752) will be evaluated
  • Experimental: Substudy-6B
    Data-DXd in combination with rilvegostomig (AZD2936) will be evaluated
  • Experimental: Substudy-6C
    Dato-DXd will be evaluated as monotherapy
  • Experimental: Substudy-6D
    Dato-DXd in combination with carboplatin or cisplatin will be evaluated
  • Experimental: Substudy-7A
    Dato-DXd will be evaluated as monotherapy

Geprüfte Regime

  • Datopotamab deruxtecan (Dato-DXd) (DS-1062a):
    Intravenous (IV) Antibody drug conjugate
  • Capecitabine (Xeloda):
    Administered orally
  • 5-Fluorouracil (Adrucil):
    Administered as an IV
  • Volrustomig (MEDI5752):
    Administered as an IV
  • Carboplatin (Paraplatin):
    Administered as an IV
  • Leucovorin LV (Folinic acid):
    Administered as an IV
  • Bevacizumab (Avastin):
    Administered as an IV
  • Rilvegostomig (AZD2936):
    Administered as an IV
  • Prednisone/ prednisolone (Prednisolone):
    Administered orally
  • Cisplatin (Platinol):
    Administered as an IV

Quelle: ClinicalTrials.gov


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