Trial Title:
A Study to Explore Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of Novel Therapeutics in Patients With Early Relapsed Metastatic Triple-negative Breast Cancer
NCT ID:
NCT06508216
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Durvalumab
Conditions: Keywords:
early relapsed metastatic
triple negative breast cancer
HER2 negative
Hormone-receptor negative breast cancer
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
COMPASS-TNBC is a single-center, open-label, modular phase 1b/2 trial assessing the
safety and efficacy of innovative therapies and combinations in patients with early
relapsed advanced TNBC. The study is of modular design allowing assessment of safety,
tolerability, and antitumor activity of multiple modules combining a wide range of
different compounds. New combination treatment modules could be added during the study,
via a protocol amendment. The combination module will be composed of 2 parts: a
dose-finding part (Part 1) based on study drugs dose escalation and de-escalation and a
dose-expansion part (Part 2) based on the RP2D found in Part 1. Modules for which the
RP2D is already determined will be composed only of a dose-expansion part (Part 2).
Therefore, the first 2 modules (Module 1: Dato-DXd single agent and Module 2: Dato-DXd +
Durvalumab) will be composed only of part 2.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dato-DXd
Description:
Patients in module 1 & 2 will receive Datopotamab Deruxtecan (Dato-DXd) 6mg/kg every 21
days
Arm group label:
Module 1 of part 2 : Datopotamab Deruxtecan (Dato-DXd) Monotherapy
Arm group label:
Module 2 of part 2 : Datopotamab Deruxtecan (Dato-DXd) + Durvalumab
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
Patients in module 2 only will receive Durvalumab 1120mg every 21 days
Arm group label:
Module 2 of part 2 : Datopotamab Deruxtecan (Dato-DXd) + Durvalumab
Summary:
Choice Of the Most Active Strategies for Short term recurring Triple Negative Breast
Cancer:
A phase Ib/II, open-label, modular, dose-finding and dose-expansion study to explore
safety, tolerability, pharmacokinetics, and anti-tumor activity of novel therapeutics in
patients with early relapsed metastatic triple-negative breast cancer
Detailed description:
Every year, approximately 170.000 women are diagnosed with triple negative breast cancer
(TNBC) and about 80-85% present with a stage II or III tumor making them eligible to
neoadjuvant chemotherapy (NACT). Despite the substantial outcome improvements achieved
with neoadjuvant chemotherapy-based strategies, at least 50-60% of patients with TNBC do
not achieve pCR and are at higher risk of presenting with early disease recurrences.
About 40% of patients with no-pCR experience distant recurrences within 12 months from
the end of (neo)adjuvant treatments. Overall, 20-25% of patients with TNBC develop an
early recurrence at ≤ 12 months from the end of (neo)adjuvant chemotherapy. Neither
standard chemotherapy options nor approved targeted therapies exist for 35.000-40.000
women/year with TNBC (≈1200 women/year in France) that progress during (neo)adjuvant
treatment or within 1 year from its termination. These patients present a "hard-to-treat"
disease and a disproportionately high rate of morbidity and mortality. Notwithstanding,
they are excluded from most current clinical trials that evaluate the efficacy of
innovative strategies, with immunotherapy or targeting therapies in combination with
chemotherapy. The treatment algorithm in 1st line is often based on the use of
platine-containing regimens that provide very low response rates (less than 15%), no more
than 2-3 months of 1st-line PFS and a median OS of about 9 months. Yet, comprehensive
genomic analyses performed over the past years on patients with residual disease after
neoadjuvant chemotherapy have not introduced concrete findings for guiding drug
development in this setting. Comparisons of initial biopsies with post-NACT tumor tissues
revealed a wide range of profound tumor changes acquired under the selective pressure of
NACT that encompass the development of dominant subclones, tumor immune depletion and
stem-cell phenotype enrichment that cannot be addressed with a single treatment strategy.
Therefore, it is necessary to explore a broad range of treatment approaches to cover the
different patterns involved. The idea is to set a rapidly recruiting phase I-II trials
allowing to explore new treatment-strategies in patients with early recurrent and highly
refractory TNBC have the potential to fulfil this utmost and urgent medical need.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female patients (who are ≥18 years of age at the time of signing the
informed consent) who have a pathologically documented breast cancer that is:
- Advanced/unresectable (patients who can be treated with curative intent are not
eligible) or metastatic.
- HER2-negative (IHC 0, 1+ or IHC 2+/ISH-) based on local assessment according to
ASCO/CAP guidelines 1.
- Documented as hormone receptor-negative (both oestrogen receptors and
progesterone receptors are negative [oestrogen receptors and progesterone
receptors < 10%]) as per GEFPICS guidelines in the metastatic setting 2.
2. Patients need to provide an adequate tissue sample: provided from either a new
biopsy of a metastatic site or the most recent archival biopsy taken at the time of
diagnosis of metastatic disease, if performed within 1 month of the ICF signature.
Additionally, an archival sample of the primary tumor may be submitted (if
available) in addition to any recent archival tissue provided.
3. Patients who have early relapsed triple negative breast cancer i.e.:
- Patients who have received neo/adjuvant chemotherapy in the localized stage.
- Radiological and anatomopathological evidence of disease recurrence or
metastasis while on (neo)adjuvant treatment or within 12 months from the end of
all treatments with curative intent.
4. Patients with germinal pathological BRCA1/2 mutations are eligible to the study if
they have received prior treatment with PARP inhibitor.
5. ECOG PS of 0 to 2.
6. LVEF ≥ 50% within 28 days before enrolment.
7. Adequate organ and bone marrow function within 14 days prior to treatment
assignment.
8. At least one lesion, not previously irradiated (and different from the biopsy site),
that qualifies as a RECIST 1.1 target lesion at baseline.
9. An adequate treatment washout period before randomization/enrolment.
10. Patients with leptomeningeal or brain metastases can be included in the trial if
symptoms are controlled with corticosteroids until 10 mg/day of prednisone or
equivalent. Patients with brain metastases must receive radiotherapy if indicated,
before study entry. Anticonvulsant therapy must be stable for at least 14 days prior
to C1D1.
Reproduction
11. Evidence of post-menopausal status or negative serum pregnancy test for females of
child-bearing potential who are sexually active with a non-sterilized male partner.
For women of child-bearing potential, a negative result for a pregnancy test (A
negative serum pregnancy test at screening visit and a negative serum or urine
pregnancy test within 72 hours prior to first study treatment administration).
Women will be considered post-menopausal if they have been amenorrhoeic for at least
12 months without an alternative medical cause. The following age-specific
requirements apply:
- Women < 50 years of age would be considered post-menopausal if they have been
amenorrhoeic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating
hormone levels in the post-menopausal range for the institution.
- Women ≥ 50 years of age would be considered post-menopausal if they have been
amenorrhoeic for 12 months or more following cessation of all exogenous
hormonal treatments, had radiation-induced menopause with last menses> 1 year
ago, had chemotherapy-induced menopause with last menses > 1 year ago).
12. Women who are surgically sterile (i.e., bilateral salpingectomy, bilateral
oophorectomy, or complete hysterectomy) are eligible.
13. Female patients of child-bearing potential who are sexually active with a
non-sterilized male partner must use at least one highly effective method of
contraception from the time of screening and must agree to continue using such
precautions for 7 months after the last dose of study treatment. Not all methods of
contraception are highly effective. Female patients must refrain from egg cell
donation and breastfeeding while on study and for 7 months after the last dose of
study treatment. Not engaging in sexual activity for the duration of the study and
drug washout period is an acceptable practice; however, periodic, or occasional
abstinence, the rhythm method, and the withdrawal method are not acceptable methods
of contraception.
14. Non-sterilized male patients who are sexually active with a female partner of
child-bearing potential must use a condom with spermicide from screening to 4 months
after the final dose of study treatment. Not engaging in sexual activity for the
duration of the study and drug washout period is an acceptable practice; however,
periodic, or occasional abstinence, the rhythm method, and the withdrawal method are
not acceptable methods of contraception. It is strongly recommended for the female
partners of a male patient to also use at least one highly effective method of
contraception throughout this period. In addition, male patients should refrain from
fathering a child or donating sperm during the study and for 4 months after the last
dose of study treatment. Preservation of sperm should be considered prior to
enrollment in this study.
15. Female patients must not donate, or retrieve for their own use, ova from the time of
screening and throughout the study treatment period, and for at least 7 months after
the final study treatment administration. Preservation of ova should be considered
prior to enrollment in this study Informed Consent
16. Patient must understand, sign and date the written informed consent form (ICF) prior
to any protocol-specific procedures performed. Patient should be able and willing to
comply with study visits and procedure as per protocol.
17. Patient must be affiliated to a social security system or beneficiary of the same.
Exclusion Criteria:
1. Evidence of untreated spinal cord compression or with leptomeningeal or brain
metastases, requiring more than 10 mg/day of prednisone or equivalent.
Note: Untreated spinal cord compression: patients can enter the study after adequate
treatment of spinal cord compression.
2. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, uncontrolled or significant cardiovascular disease, severe pulmonary
function compromise, serious chronic gastrointestinal conditions associated with
diarrhea, or psychiatric illness/social situations that would limit compliance with
study requirements, substantially increase risk of incurring AEs or compromise the
ability of the patient to give written informed consent.
3. Has a clinically significant corneal disease.
4. Has a history of non-infectious ILD/pneumonitis including radiation pneumonitis that
required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis
that cannot be ruled out by imaging at screening.
5. Uncontrolled or significant lung disease or prior pneumonectomy.
6. Active connective tissue or inflammatory disorders requiring treatment, or active or
prior documented autoimmune disease within the past 5 years. Of note, patients with
vitiligo, Grave's disease or psoriasis not requiring systemic treatment (within the
past 2 years) are not excluded. Patients with type 1 diabetes or hypothyroidism
stable under treatment or not requiring systemic treatment are eligible.
7. Active primary immunodeficiency.
8. Has active or uncontrolled hepatitis B or C virus infection.
Patients are eligible if they:
1. Have been curatively treated for HCV infection as demonstrated clinically and
by viral serologies
2. Have received HBV vaccination with only anti-HBs positivity and no clinical
signs of hepatitis
3. Are HBsAg- and anti-HBc+ (i.e., those who have cleared HBV after infection) and
meet conditions i-iii of criterion d below:
4. Are HBsAg+ with chronic HBV infection (lasting 6 months or longer) and meet
conditions i-iii below:
i. HBV DNA viral load < 2000 IU/mL ii. Have normal transaminase values, or, if liver
metastases are present, abnormal transaminases, with a result of AST/ALT <5× ULN,
which are not attributable to HBV infection iii. Start or maintain antiviral
treatment if clinically indicated as per the investigator
9. Patients with known controlled HIV infection and undetectable HIV-DNA are eligible
to the trial.
Note: all of the following criteria are required to define an HIV infection that is
well controlled: undetectable viral RNA, CD4+ count ≥ 350, no history of
AIDS-defining opportunistic infection within the past 12 months, and stable for at
least 4 weeks on the same anti-HIV medications (meaning there are no expected
further changes in that time to the number or type of antiretroviral drugs in the
regimen). If an HIV infection meets the above criteria, monitoring of viral RNA load
and CD4+ count is recommended. Patients must be tested for HIV during the screening
period if acceptable by local regulations or an institutional review board
(IRB)/ethics committee (EC).
10. Any concurrent systemic therapy (e.g. chemotherapy, targeted therapy,
immunotherapy..), radiotherapy, investigational agent , or biological therapy for
cancer treatment. Concurrent use of hormonal therapy for non-cancer-related
conditions (e.g., hormone replacement therapy) is acceptable.
11. History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease ≥ 5
years before the first dose of study treatment.
2. Adequately treated non-melanoma skin cancer or Lentigo maligna without evidence
of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
12. Has a history of severe hypersensitivity reactions to either the study treatment(s)
or inactive ingredients (including but not limited to polysorbate 80 of Dato-DXd),
or has a history of severe hypersensitivity reactions to other monoclonal
antibodies.
13. Patients having received prior treatment with any antibody drug conjugates targeting
TROP2 (eg, Sacituzumab govitecan) are not eligible to the study.
14. Judgment by the Investigator that the patients should not participate in the study
if the patient is unlikely to comply with study procedures, restrictions, and
requirements.
15. History of allogeneic organ transplantation.
16. Patient has clinically significant, uncontrolled heart disease and/or recent cardiac
events including any of the following:
1. History of angina pectoris, coronary artery bypass graft (CABG), symptomatic
pericarditis, or myocardial infarction within 12 months prior to the start of
study treatment.
2. History of documented congestive heart failure (New York Heart Association
functional classification III-IV).
3. Documented cardiomyopathy.
4. Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by
Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO).
5. History of any cardiac arrhythmias (e.g., ventricular tachycardia), complete
left bundle branch block, high grade AV block (e.g., bifascicular block, Mobitz
type II and third degree AV block), supraventricular, nodal arrhythmias, or
conduction abnormality in the previous 12 months.
6. Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mmHg
and/or Diastolic Blood Pressure (DBP) ≥ 100 mmHg, with or without
antihypertensive medication. Initiation or adjustment of antihypertensive
medication(s) is allowed prior to screening.
17. Patients with prior use of immunosuppressive medications within 14 days prior to
first study drug dose or anticipation of need for systemic immunosuppressive
medication during study treatment, except for intranasal and inhaled corticosteroids
or systemic corticosteroids at doses less than 10 mg/day of prednisone or
equivalent.
18. Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 7 months after the last dose of study treatment. (See contraception
requirements outlined in Appendix 7 of this protocol).
19. Administration of live attenuated vaccines within 30 days prior to the first dose of
study treatment, or anticipation that such a live, attenuated vaccine will be
required during the study or within 3 months after the last dose of study treatment.
20. Persons deprived of their freedom or under guardianship, or for whom it would be
impossible to undergo the medical follow-up required by the trial, for geographic,
social or psychological reasons.
21. Participation in another clinical study with an investigational product during the
last 4 weeks prior to enrollment and while on study treatment.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Country:
France
Status:
Recruiting
Contact:
Last name:
Barbara Pistilli, MD
Email:
BARBARA.PISTILLI@gustaveroussy.fr
Contact backup:
Last name:
Thomas Grinda, MD
Email:
thomas.grinda@gustaveroussy.fr
Start date:
July 5, 2024
Completion date:
December 17, 2027
Lead sponsor:
Agency:
Gustave Roussy, Cancer Campus, Grand Paris
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
Gustave Roussy, Cancer Campus, Grand Paris
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06508216
