AzTrials
AzTrials

Breast CancerPhase 1/2COMPASS-TNBCNCT06508216

A Study to Explore Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of Novel Therapeutics in Patients With Early Relapsed Metastatic Triple-negative Breast Cancer

A Phase 1/2 study testing Dato-DXd and Durvalumab in people with Breast Cancer, run by Gustave Roussy, Cancer Campus, Grand Paris at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Dato-DXd and Durvalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteFrance
Study dates
5 Jul 2024to 17 Dec 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • Patients who have early relapsed triple negative breast cancer i.e.:
Show all 27Show fewer
  • 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.
  • Patients with germinal pathological BRCA1/2 mutations are eligible to the study if they have received prior treatment with PARP inhibitor.
  • ECOG PS of 0 to 2.
  • LVEF ≥ 50% within 28 days before enrolment.
  • Adequate organ and bone marrow function within 14 days prior to treatment assignment.
  • At least one lesion, not previously irradiated (and different from the biopsy site), that qualifies as a RECIST 1.1 target lesion at baseline.
  • An adequate treatment washout period before randomization/enrolment.
  • 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
  • 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).
  • Women who are surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) are eligible.
  • 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.
  • 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.
  • 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
  • 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.
  • Patient must be affiliated to a social security system or beneficiary of the same.

Who cannot join

  • 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.
  • 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.
  • Has a clinically significant corneal disease.
  • 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.
  • Uncontrolled or significant lung disease or prior pneumonectomy.
Show all 38Show fewer
  • 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.
  • Active primary immunodeficiency.
  • Has active or uncontrolled hepatitis B or C virus infection.
  • Patients are eligible if they:
  • Have been curatively treated for HCV infection as demonstrated clinically and by viral serologies
  • Have received HBV vaccination with only anti-HBs positivity and no clinical signs of hepatitis
  • Are HBsAg- and anti-HBc+ (i.e., those who have cleared HBV after infection) and meet conditions i-iii of criterion d below:
  • Are HBsAg+ with chronic HBV infection (lasting 6 months or longer) and meet conditions i-iii below:
  • 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
  • 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).
  • 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.
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study treatment.
  • Adequately treated non-melanoma skin cancer or Lentigo maligna without evidence of disease.
  • Adequately treated carcinoma in situ without evidence of disease.
  • 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.
  • Patients having received prior treatment with any antibody drug conjugates targeting TROP2 (eg, Sacituzumab govitecan) are not eligible to the study.
  • 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.
  • History of allogeneic organ transplantation.
  • Patient has clinically significant, uncontrolled heart disease and/or recent cardiac events including any of the following:
  • History of angina pectoris, coronary artery bypass graft (CABG), symptomatic pericarditis, or myocardial infarction within 12 months prior to the start of study treatment.
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV).
  • Documented cardiomyopathy.
  • Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO).
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • Participation in another clinical study with an investigational product during the last 4 weeks prior to enrollment and while on study treatment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Thomas Grinda, MD contact

+33 1 42 11 42 11

thomas.grinda@gustaveroussy.fr

Chloé Serhal, PhD contact

+33 1 42 11 42 11 ext. 23 43

chloe.serhal@gustaveroussy.fr

France1 site, 1 recruiting

  • Gustave Roussy

    Villejuif

    Barbara Pistilli, MD, BARBARA.PISTILLI@gustaveroussy.fr

    Thomas Grinda, MD, thomas.grinda@gustaveroussy.fr

    Recruiting

Other trials in France

About this study

Official title: 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

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

Read the 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.

Conditions
Breast Cancer
Being tested
Dato-DXd, Durvalumab
Keywords
early relapsed metastatic, triple negative breast cancer, HER2 negative, Hormone-receptor negative breast cancer
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dato-DXdDrug

    Patients in module 1 \& 2 will receive Datopotamab Deruxtecan (Dato-DXd) 6mg/kg every 21 days

  • DurvalumabDrug

    Patients in module 2 only will receive Durvalumab 1120mg every 21 days

Study groups in NCT06508216
Study groupRoleWhat they receive
Module 1 of part 2 : Datopotamab Deruxtecan (Dato-DXd) MonotherapyExperimentalPatients will receive Datopotamab Deruxtecan 6mg/kg every 21 days until progression or until unacceptable toxicity
Receives: Drug: Dato-DXd
Module 2 of part 2 : Datopotamab Deruxtecan (Dato-DXd) + DurvalumabExperimentalPatients will receive Datopotamab Deruxtecan 6mg/kg and durvalumab 1120mg every 21 days until progression or until unacceptable toxicity
Receives: Drug: Dato-DXd; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 2_Efficacy of study therapies in each module_objective response rate (ORR) at 6 months.

    ORR is defined as the proportion of patients who achieved a confirmed CR or PR within the 6 months of treatment initiation assessed by investigators.

    Measured: Within the 6 months of treatment initiation

  2. Part 1_Safety and to determine the recommended phase II dose (RP2D) of study therapies in each module

    measured by the DLTs, frequency and severity of any AEs, TEAEs, SAEs, AESIs graded according to NCI-CTCAE v5.0, proportion of treatment discontinuations, interruptions, and dose reductions due to any AEs; frequency and severity of laboratory abnormalities defined by NCI-CTCAE v5.0

    Measured: During treatment_to be determined according to modules added later on

Secondary outcomes (12)

  1. Part 1&2_Progression free survival (PFS)

    Defined as the time from the date of first dose until the date of the first objective documentation of disease progression or death from any cause, whichever occurs first. For patients without documented radiological progression, PFS will be censored at the date of last adequate radiological assessment without progression, unless death occurs within ≤ 2 missing assessments following the date of last known progression-free, in which case the death will be counted as a PFS event.

    Measured: From the time date of the first dose until progression or death from any cause, whichever occurs first

  2. Part 1&2_Duration of response (DOR)

    Defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progression (PD) or death due to any cause, whichever occurs first. Duration of response will be measured for responding patients (CR or PR) only.

    Measured: From cycle 3 (Week 6; each cycle is 28 days) up to 2 years after the EoT, an average of 33 months

  3. Part 1&2_Clinical benefit rate (CBR)

    Defined as the proportion of patients with a complete (CR) or partial response (PR) or with stable disease (SD) > 6 months.

    Measured: During treatment period, a median of 6 months

  4. Part 1&2_Overall survival (OS)

    Defined as the time from the date of first dose until death. Patients alive at last follow-up will be censored at this date.

    Measured: From the date of the first dose until 24 months after EoT

  5. Part 2_Frequency of all adverse events

    Measured: From enrollment to 30 days after EoT for module 1 and for 90 days for module 2

  6. Part 2_Severity of all adverse events

    As defined by the NCI-CTCAE v5.0.

    Measured: From enrollment to 30 days after Eo for module 1 and for 90 days for module 2

  7. Part 2_Frequency of laboratory abnormalities

    Measured: From enrollment until progression, median of 6 months

  8. Severity of laboratory abnormalities

    Defined by NCI-CTCAE v5.0

    Measured: From enrollment until progression, median of 6 months

  9. Proportion of treatment discontinuation due to any AEs.

    Measured: Treatment Period, median of 6 months

  10. Proportion of treatment interruptions due to any AEs.

    Measured: Treatment Period, median of 6 months

  11. Proportion of dose reductions due to any AEs.

    Measured: Treatment Period, median of 6 months

  12. Part 1_efficacy of study therapies in each module_objective response rate (ORR)

    ORR is defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) assessed by investigators. The objective response will be radiologically assessed every 6 weeks using RECIST v1.1.

    Measured: Within the 6 months of treatment initiation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2024
  2. Study start5 Jul 2024
  3. Primary completion17 Dec 2025 (estimated)
  4. Study completion17 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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.
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06508216
Sponsor's protocol ID
2023-503606-36-00
Other IDs
2022/3571, 2023
Acronym
COMPASS-TNBC
Status last verified
Jul 2024
First submitted
3 Jul 2024
Last updated
22 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dato-DXd and Durvalumab in people with Breast Cancer, run by Gustave Roussy, Cancer Campus, Grand Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Thomas Grinda, MD (+33 1 42 11 42 11, thomas.grinda@gustaveroussy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 2_Efficacy of study therapies in each module_objective response rate (ORR) at 6 months. (time frame: Within the 6 months of treatment initiation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06508216.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
COMPASS-TNBC Clinical Trial NCT06508216 | AzTrials