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

NCT06508216 | Recruiting Phase 1

• 2 other identifiers: 2023-503606-36-002022/3571
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Breast Cancer

Keywords

early relapsed metastatic; triple negative breast cancer; HER2 negative; Hormone-receptor negative breast cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  Within the 6 months of treatment initiation

• 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

  During treatment_to be determined according to modules added later on

Secondary Outcomes (12)

• Part 1&2_Progression free survival (PFS)

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

• Part 1&2_Duration of response (DOR)

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

• Part 1&2_Clinical benefit rate (CBR)

  During treatment period, a median of 6 months

• Part 1&2_Overall survival (OS)

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

• Part 2_Frequency of all adverse events

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

Study Arms (2)

Module 1 of part 2 : Datopotamab Deruxtecan (Dato-DXd) Monotherapy

EXPERIMENTAL

Patients will receive Datopotamab Deruxtecan 6mg/kg every 21 days until progression or until unacceptable toxicity

Drug: Dato-DXd

Module 2 of part 2 : Datopotamab Deruxtecan (Dato-DXd) + Durvalumab

EXPERIMENTAL

Patients will receive Datopotamab Deruxtecan 6mg/kg and durvalumab 1120mg every 21 days until progression or until unacceptable toxicity

Drug: Dato-DXd; Drug: Durvalumab

Interventions

Dato-DXd DRUG

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

Module 1 of part 2 : Datopotamab Deruxtecan (Dato-DXd) Monotherapy; Module 2 of part 2 : Datopotamab Deruxtecan (Dato-DXd) + Durvalumab

Durvalumab DRUG

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

Module 2 of part 2 : Datopotamab Deruxtecan (Dato-DXd) + Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• AstraZeneca: collaborator

Study Sites (1)

Gustave Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Triple Negative Breast Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Barbara Pistillli, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY DIRECTOR

Central Study Contacts

Thomas Grinda, MD

CONTACT

+33 1 42 11 42 11; thomas.grinda@gustaveroussy.fr

Chloé Serhal, PhD

CONTACT

+33 1 42 11 42 11; chloe.serhal@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: July 18, 2024
• Study Start: July 5, 2024
• Primary Completion: December 17, 2025
• Study Completion (Estimated): December 17, 2027
• Last Updated: July 22, 2024

Record last verified: 2024-07

Locations

FR (1)