E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Triple Negative Breast Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Breast Cancer not dependent on hormones |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072737 |
E.1.2 | Term | Advanced breast cancer |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the anti-tumor activity of MCS110 combined with carboplatin/gemcitabine (carbo/gem) compared to carbo/gem alone. |
|
E.2.2 | Secondary objectives of the trial |
1. Characterize the safety and tolerability of MCS110 given in combination with carbo/gem.
2. Characterize PK of MCS110 when combined with carbo/gem.
3. Characterize PK of carbo and gem in the presence and absence of MCS110.
4. Characterize PD effect of MCS110 when combined with carbo/gem
5. To assess the anti-tumor activity of MCS110 given in combination with carbo/gem as measured by additional efficacy measures. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult women (≥ 18 years of age) with advanced TNBC.
- Histological or cytological evidence of estrogen-receptor negative
(ER-), progesterone receptor negative (PgR-) and human epidermal
growth factor-2 receptor negative (HER2-) BC by local laboratory
testing, based on last available tumor tissue.
- ER/PgR negativity to follow local guidelines
- If IHC HER2 2+, a negative FISH test is required
A pre-treatment tumor biopsy demonstrating high TAM content as
assessed per the central laboratory.
- Patients must have:
- At least one measurable lesion per RECIST 1.1. (Note:
Measurable lesions include lytic or mixed (lytic + blastic) bone lesions,
with an identifiable soft tissue component that meets the measurability
criteria)
or
- Bone lesions: non-measurable lytic or mixed (lytic + blastic) in
the absence of measurable disease as defined above. Patients with only
non-measurable lesions (e.g. pleural effusion, ascites) and no lytic or
mixed bone lesions are not eligible.
Other inclusion criteria may apply |
|
E.4 | Principal exclusion criteria |
- Prior chemotherapy for advanced BC. Previous adjuvant/neoadjuvant
chemotherapy is allowed (carboplatin, cisplatin or gemcitabine only if >
12 months has passed since last administration).
- Therapy for underlying malignancy within 2 weeks prior to start of
study treatment:
- Chemotherapy, biologic therapy (antibodies and biologically
targeted small molecules)
- Radiotherapy
- Major surgery
- Patients receiving concomitant immunosuppressive agents or chronic
corticosteroids (≥10 mg of prednisone or equivalent) at the time of first
dose of study drug.
- Known history of human immunodeficiency virus or active infection
with hepatitis virus or any uncontrolled active systemic infection.
- Patients with the following laboratory values during screening and on
Day 1 pre-dose:
- Absolute Neutrophil Count (ANC) < 1.5x10^9/L
- Hemoglobin < 9 g/dL
- Platelets < 100x10^9/L
- Serum creatinine > 1.5 x ULN
- Serum total bilirubin > 1.5 x ULN
- AST/SGOT and ALT/SGPT > 3.0 x ULN
Other exclusion criteria may apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
PFS as per RECIST v1.1 (by local investigator assessment) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor evaluation at sreening and then every six weeeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8). |
|
E.5.2 | Secondary end point(s) |
1. Safety: adverse event (AEs), serious adverse events (SAEs) Tolerability: Dose interruptions, reductions and dose intensity
2. Serum concentration of free MCS110 and derived PK parameters
3. Plasma concentration of carboplatin, gemcitabine and dFdU (the primary metabolite of gem), and derived PK parameters
4. Total CSF-I circulating levels, serum CTX-I and circulating monocytes in blood. TAM and TIL content in pre- and post-dose tumor biopsies
5. Tumor response per RECIST v1.1 (by local investigator assessment):
Overall Response Rate (ORR), Duration of Response (DOR), Clinical Benefit Rate (Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) ≥ 6 months). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Continuously
2. Please refer to protocol section 7
3. Please refer to protocol section 7
4. Please refer to protocol section 7
5. ORR:Tumor evaluation at screening and then every six weeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8).
DOR: Tumor evaluation at screening and then every six weeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8).
Clinical benefit rate: Tumor evaluation at screening and then every six weeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8). |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
carboplatin , gemcitabine |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Czech Republic |
France |
Germany |
Hong Kong |
Korea, Republic of |
Spain |
Taiwan |
Turkey |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of study will be upon the last patient's completion of safety follow-up. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |