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

Recruiting now · Phase 1/Phase 2

Conditions studied: Breast Cancer

In brief

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

Key facts

Study ID

NCT06508216

Run by

Gustave Roussy, Cancer Campus, Grand Paris

People needed

50

Starts

2024-07-05

Expected to finish

2027-12-17

Last updated by the study team

2024-07-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.:
• 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

You may not qualify if…

• 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.
• 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:
• 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
• 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.

Where it is running

• Gustave Roussy — Villejuif, France (enrolling)

Full record on ClinicalTrials.gov

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