Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Sacituzumab govitecan · 21 trials · 30 indications
no invasive tumour in breast and lymph nodes (ypT0/is and ypN0)
time from date of first diagnosis to any invasive breast cancer event, death or secondary malignancy according to STEEP 2.0 criteria
ORR is defined as the number of patient with at least a confirmed complete response (CR) or partial response (PR), based on the best objective response values while on treatment
EFS after 36 months defined as time from registration to any invasive breast cancer event, death, or secondary malignancy (same definition as iDFS) according to STEEP 2.0 criteria \[103\]
EFS after 36 months defined as time from registration to any invasive breast cancer event, death, or secondary malignancy or local progress precluding surgery in neoadjuvant treated patients
pCR defined as no invasive disease in breast and lymph nodes (ypT0/is, ypN0) in patients of both arms
OS is defined as length of time from randomization until the date of death from any cause.
iDFS is defined as time from randomization until first iDFS event: local invasive recurrence following mastectomy, local invasive recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral invasive breast cancer, second non-breast primary cancer (excluding squamous or basal cell carcinoma of the skin), or death from any cause. (according to Hudis (J Clin Oncol 2007) ) There will be one interim analysis for efficacy after 2/3 of the events to allow for early stopping of the trial due to overwhelming efficacy.
PFS was defined as the time from randomization until objective tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death, whichever came first. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (greater than or equal to \[≥\] 20%) in the sum of the target lesions or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate.
To evaluate the rate of disease control at 12 weeks for patients with extensive stage small cell lung cancer treated with Sacituzumab govitecan (SG) plus atezolizumab or durvalumab as maintenance therapy after induction treatment with chemotherapy and immunotherapy. Disease Control at 12 weeks is defined as a best response by RECIST 1.1 of CR, PR, non-CR, non-PR, or stable disease assessed by RECIST 1.1 and reported within 12 weeks (+/- 2 weeks) from the initiation of study therapy. Participants not known to have disease control at 12 weeks will be coded as lacking disease control.
The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria.
The rate of patients with grade ≥ 2 diarrhea is defined as the number of patients with diarrhea grade 2 to 5 the first 2 cycles of treatment by the number of patients in the analysis set per 100. The adverse events will be assessed by the Investigator and with severity determined using defined and graded according CTCAE v.5.0. The adverse events without the severity grade reported will be considered as grade 3.
The rate of patients with grade ≥ 3 neutropenia is defined as the number of patients with neutropenia grade 3 to 5 the first 2 cycles of treatment by the number of patients in the analysis set per 100. The adverse events will be assessed by the Investigator and with severity determined using defined and graded according CTCAE v.5.0. The adverse events without the severity grade reported will be considered as grade 3.
Number and identification of altered/mutated genes in the tumors in the subgroup of patients with a longer PFS on SG post T-DXd compared to the tumors in the subgroup of patients with a shorter PFS on SG post T-DXd.
To determine investigator-assessed disease-free survival (DFS) at 6 months.
Compare PFS of patients randomized to receive sacituzumab govitecan in combination with pembrolizumab (Arm A) versus those randomized to receive sacituzumab govitecan monotherapy (Arm B). Defined as the time from study randomization to disease progression, per RECIST 1.1 or medical judgment, the latter based on established clinical parameters, such as rising tumor markers and physical exam evidence of progression, i.e. worsening chest wall disease, or death due to any cause, whichever occurred first.
Subjects who achieve ≥50% PSA decline at or before 9 weeks of therapy with Sacituzumab Govitecan (IMMU-132) are considered to have responded. PSA responses will be analyzed by descriptive statistics and summarized in tabular format (frequency tables). The overall PSA response rate will be reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method.
Proportion of participants remaining alive and progression free (using Prostate Cancer Working Group 2 (PCWG2) criteria) 6 months from time of starting treatment as estimated by the Kaplan-Meier method.
The Maximum Tolerated Dose (MTD) in mg of Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) in Combination is assessed.
Treatment-Related Adverse Events are assessed by CTCAE v5.0 when administering Sacituzumab Govitecan (SG) and Enfortumab Vedotin (EV) in combination.
Study SG + EV combination to further refine the recommended dose and to assess the ORR (unconfirmed CR or PR) per RECIST Version 1.1 as determined by investigator for the combination of EV and SG in combination in patients with mUC progressing on platinum-based chemotherapy and PD1/L1 inhibitors.
Study SG + EV + Pembrolizumab in combination to assess the ORR (unconfirmed CR or PR) per RECIST Version 1.1 as determined by investigator for the combination therapy of Pembrolizumab in combination with EV and SG in treatment-naïve patients with mUC.
To establish the safety, tolerability, and feasibility of bladder preservation therapy treatment with concurrent SG and adaptive image-guided radiation therapy for patients with localized MIBC. This will be assessed by estimating the rate of acute dose-limiting toxicities occurring during Cycles 2-3 of treatment.
Levels of SN-38 and its metabolites will be measured and a ratio calculated relative to the serum concentration of SN-38 and its metabolites. The ratio will show the amount of investigational product that crosses the blood brain barrier to reach the tumor.
| Arm | Type | Description |
|---|---|---|
| Neoadjuvant treatment: 12 weeks (4 cycles) SG i.v. | EXPERIMENTAL | * Cohort 1a: In case of (near) cCR: end of treatment, followed by surgery * Cohort 1b: In case of cPR after 12 weeks: further 6 weeks (2 cycles) SG i.v., followed by surgery (use of core biopsy is allowed per investigator´s decision, if further NACT is planned) pCR dependent post-neoadjuvant treatment * In case of pCR: no further systemic treatment * In case of non-pCR: chemotherapy according to investigators decision, e.g., AC/EC q3w x 4, PAC/Carbo q1w x 12 |
| Neoadjuvant treatment: 12 weeks (4 cycles) SG+PEM i.v. | EXPERIMENTAL | * Cohort 2a: In case of (near) cCR: end of treatment, followed by surgery * Cohort 2b: In case of cPR after 12 weeks: 6 weeks (2 cycles) SG+PEM i.v., followed by surgery (use of core biopsy is allowed per investigator´s decision, if further NACT is planned) pCR dependent post-neoadjuvant treatment * In case of pCR: no further systemic treatment * In case of non-pCR: chemotherapy according to investigators decision, e.g., AC/EC q3w x 4, PAC/Carbo q1w x 12 |
| Single arm receiving sacituzumab govitecan | EXPERIMENTAL | - |
| Cohort I (non-randomized) | OTHER | Cohort I will include patients with clinical stage II disease at baseline who have a cCR after up to 12 weeks of NACT with CARBO/PAC and PEM. After surgery, patients with a pCR (ypT0/is, ypN0) will not receive further chemotherapy (CTx) but continue on SoC treatment according to current valid treatment guidelines for breast cancer at investigator´s discretion. Patients with residual disease should be considered for postoperative SoC treatment, which may include further CTx (e.g., AC/EC x 4, q2w or q3w or Capecitabine) plus PEM or Olaparib (in patients with gBRCA mutations) according to current valid treatment guidelines for breast cancer and per investigator´s discretion. |
| Cohort II (randomized) - Sacituzumab govitecan + pembrolizumab (SG+PEM) | EXPERIMENTAL | neoadjuvant SG+PEM (4 cycles), followed by surgery and pCR-dependent post-neoadjuvant SoC treatment according to current valid treatment guidelines for breast cancer and per investigator´s discretion. |
| Cohort II (randomized) - Standard-of-care chemotherapy + pembrolizumab (SoC CTx+PEM) | ACTIVE_COMPARATOR | SoC, e.g., AC x 4 + PEM or EC x 4 + PEM, followed by surgery and pCR-dependent post-neoadjuvant SoC treatment, e.g., AC x 4 \* PEM or EC x 4 + PEM, or Capecitabine + PEM or Olaparib (in patients with gBRCA mutations), according to current valid treatment guidelines for breast cancer and per investigator´s discretion. |
| Treatment Group A: SG | EXPERIMENTAL | Participants assigned to treatment group A will receive SG 10 mg/kg intravenous (IV) infusion on Days 1 and 8 of a 21-day cycle. Participants will receive study drug until progressive disease (PD), death, unacceptable toxicity, or another treatment discontinuation criterion is met. |
| Treatment Group B: Topotecan, or Lurbinectedin, or Amrubicin | EXPERIMENTAL | Participants assigned to Treatment Group B will receive one of the following investigator selected treatments within a 21 day cycle: * Topotecan 1.5 mg/m² administered daily on Days 1 through 5, or * Lurbinectedin 3.2 mg/m² administered as an intravenous infusion on Day 1 (in countries/regions where lurbinectedin is approved and available). In Japan, participants assigned to Treatment Group B may alternatively receive: • Amrubicin (available only in Japan) 40 mg/m² administered daily on Days 1 through 3 of a 21 day cycle. Study treatment will continue until disease progression, death, unacceptable toxicity, or another protocol defined criterion for treatment discontinuation is met. |
| Sacituzumab govitecan | EXPERIMENTAL | Sacituzumab govitecan is administered intravenously 10 mg/kg body weight on days 1, 8 q3w for eight cycles. |
| Treatment of physician´s choice | OTHER | TPC, defined as capecitabine or platinum-based chemotherapy for eight cycles or Observation. |
| Treatment of Physician's Choice (TPC) | ACTIVE_COMPARATOR | Participants will receive TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent regimen that is selected by the investigator before participant randomization. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable AEs. |
| SG and atezolizumab/durvalumab | EXPERIMENTAL | Sacituzumab govitecan 10 mg/kg via IV infusion on Day 1 and Day 8 of a 21-day cycle (ie, 2 weekly doses plus 1 week without treatment) AND Atezolizumab 1200mg via IV infusion on Day 1 of a 21-day cycle (ie, once every 3 weeks) OR Sacituzumab govitecan 10 mg/kg via IV infusion on Day 1 and Day 8 of a 21-day cycle (ie, 2 weekly doses plus 1 week without treatment) AND Durvalumab 1500mg via IV infusion on Day 1 of a 21-day cycle (ie, once every 3 weeks) |
| Sacituzumab govitecan, 10 mg/kg | EXPERIMENTAL | Sacituzumab govitecan, 10 mg/kg for the first 2 weeks of 21-day cycle until progression or adverse effects prohibit further treatment |
| Sacituzumab Govitecan + Trastuzumab (or Biosimilar) | EXPERIMENTAL | Participants will complete the following: * Baseline visit with assessments. * CT or MRI scans every 9 weeks for 27 weeks and then every 12 weeks. * Echocardiogram or MUGA scan every 12 weeks for 24 weeks and then every 16 weeks. * Cycle 1 through Cycle 2: * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily. * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily. * Cycle 2: * Day 1: Optional tumor biopsy * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily. * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily. * Cycle 3 through End of Treatment: * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily. * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily. * End of treatment: * Follow up visits every 6 months. |
| Sacituzumab Govitecan + Loperamide + G-CSF | EXPERIMENTAL | Upon meeting all selection criteria, patients enrolled in the study will receive the combination of: Sacituzumab govitecan :10 mg/kg, intravenously (IV) on Days 1 and 8 every 21-day cycle . This treatment will continue until disease progression, unacceptable toxicity, or physician's/patient's decision. Loperamide : 2 mg orally (PO), twice a day (BID), or 4 mg once a day (QD) during three consecutive days after administration of sacituzumab govitecan, (D2, D3, D4 and D9, D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician). G-CSF : 30 MU subcutaneously (SC) QD during two consecutive days, 48 hours after administration of sacituzumab govitecan (D3, D4 and D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician). |
| Sacituzumab Govitecan PLUS Nivolumab | EXPERIMENTAL | Patients eligible for this study treatment will receive combination therapy with Sacituzumab Govitecan with Nivolumab for 4 cycles, followed by single-agent Nivolumab for an additional 11 cycles. |
| Experimental | EXPERIMENTAL | Sacituzumab govitecan (10 mg/kg) administered intravenously on Days 1 and 8 of a 21-day cycle. Patients will be treated until progression, death, study withdrawal, or unacceptable toxicity. |
| Sacituzumab Govitecan (SG) Infusion | EXPERIMENTAL | SG will be administered on Days 1 and 8 of continuous 21-day cycles at 10 mg/kg via intravenous (IV) infusion until disease progression or unacceptable toxicity. |
| Sacituzumab Govitecan + Pembrolizumab | EXPERIMENTAL | Participants will receive Sacituzumab Govitecan + Pembrolizumab at a pre-determined dose during a 21 day cycle. Sacituzumab Govitecan will be given on days 1 and 8 of the 21 day cycle Pembrolizumab will be given on day 1 of the 21 day cycle. |
| Retreatment | EXPERIMENTAL | Participants randomized to the combination arm (Sacituzumab Govitecan + Pembrolizumab) who stop with CR after at least 24 weeks of treatment may be eligible for additional pembrolizumab and/or sacituzumab govitecan therapy if they progress after stopping study treatment. This is termed the Second Course Phase and is only available if the study remains open and the subject meets conditions. . |
| Sacituzumab Govitecan Treatment | EXPERIMENTAL | Subjects enrolled in this study will receive Sacituzumab Govitecan in addition to their single agent Androgen Receptor Signaling Inhibitors (ARSI) as treatment for Castrate-Resistant Prostate Cancer. Dose will be calculated per protocol in milligrams based on the subject's body weight at the beginning of each cycle or more frequently if weight changes \>10%. Subjects will be treated on days 1 and 8 in a 21-day cycle, minimum 3 cycles. |
| Dose Escalation Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) | EXPERIMENTAL | Participants will be given the study drugs Enfortumab Vedotin and then Sacituzumab Govitecan on Days 1 and 8 of a 21-day study cycle. Dose escalation and de-escalation for the Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) combination will be guided using the Bayesian optimal interval (BOIN) design with up to 4 dose level escalations. |
| Dose Expansion Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) | EXPERIMENTAL | Participants will be given the study drugs Enfortumab Vedotin and then Sacituzumab Govitecan on Days 1 and 8 of each 21-day study cycle. Three dose levels of this drug combination will be studied with 3-18 patients per dose level depending on treatment-related dose limiting toxicities. |
| Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) and Pembrolizumab | EXPERIMENTAL | Participants will be given a triplet regimen of Enfortumab Vedotin 1.25mg/kg, Sacituzumab Govitecan 7.5mg/kg (D1 and D8 every three weeks), and Pembrolizumab 200mg (D1 every 3 weeks) or 400 mg (D1 every 6 weeks) as a front-line therapy. Dose reductions of Enfortumab Vedotin to 1, 0.75 and 0.5 mg/kg will be permitted while Sacituzumab Govitecan can be dose reduced to 5 mg/kg. No dose reductions of Pembrolizumab are permitted. Following C1D1, drugs may be held independently per investigator discretion. A safety run-in will be conducted for the first 12 patients to evaluate the tolerability of the triplet regimen using Bayesian toxicity monitoring (BTOX). The first stage will enroll 6 patients, and if there are 2 or fewer DLTs, then next 6 patients will be enrolled. The study will be halted if there are 5 or more DLTs observed among the total of 12 evaluable patients. |
| SG + Adaptive radiotherapy | EXPERIMENTAL | Sacituzumab Govitecan, IV, 8 mg/kg, 21-day cycles for 1 loading cycle prior to radiation and two subsequent cycles with concurrent adaptive radiotherapy |
| Breast Brain Metastasis and Glioblastoma | EXPERIMENTAL | Sacituzumab Govitecan treatment will be initiated with a 10mg/kg standard dose without any dose escalation on day-1, prior to surgery. Sacituzumab govitecan and will continue to be administered by IV infusion over 3 hours on Days 1 and 8 of a 21 day cycle post-operatively until progression. |
| Name | Type | Description |
|---|---|---|
| Sacituzumab govitecan | DRUG | 10 mg/kg twice on Days 1 and 8 of a continuous 21-day treatment cycle |
| Pembrolizumab | DRUG | 200 mg every 3 weeks (q3w) |
| Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA] | DRUG | Pembrolizumab 200 mg will be administered as a 30-minute i.v. infusion every 3 weeks. |
| SoC Chemotherapy | DRUG | Standard of care chemotherapy as per common treatment guidelines and recommendations |
| Sacituzumab Govitecan (SG) | DRUG | Administered intravenously |
| Topotecan | DRUG | Administered intravenously |
| Amrubicin (Japan only) | DRUG | Administered intravenously |
| Lurbinectedin (regions/countries where approved and available) | DRUG | Administered intravenously |
| Capecitabine | DRUG | 2000 mg/m² day 1-14 q21 day cycle for eight cycles |
| Carboplatin | DRUG | AUC 5 q3w or AUC 1.5 weekly for eight 3 weekly cycles |
| Cisplatin | DRUG | 25mg/m3 weekly or 75 mg/m3 q3w |
| Eribulin | DRUG | Administered IV over 2 to 5 minutes at a dose 1.4 mg/m\^2 at North American sites and 1.23 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle for up to 15.3 months. Lower doses will be administered on the same schedule to participants with moderate hepatic impairment (ie, Child-Pugh B; 0.7 mg/m\^2 and 0.67 mg/m\^2 for North American and European sites, respectively). |
| Gemcitabine | DRUG | 800 to 1200 mg/m\^2 will be administered IV over 30 minutes on Days 1, 8, and 15 of a 28-day cycle for up to 8.1 months. |
| Vinorelbine | DRUG | 25 mg/m\^2 will be administered as a weekly IV injection over 6-10 minutes for up to 11.5 months. Vinorelbine will not be allowed as TPC for any participant with Grade 2 neuropathy. |
| Atezolizumab | DRUG | Atezolizumab 1200mg via IV infusion on Day 1 of a 21-day cycle (ie, once every 3 weeks) |
| Durvalumab | DRUG | Durvalumab 1500mg via IV infusion on Day 1 of a 21-day cycle (ie, once every 3 weeks) |
| Trastuzumab | DRUG | Humanized IgG1 kappa monoclonal antibody, 150mg single-dose vial, via intravenous infusion per protocol. |
| Trastuzumab and Hyaluronidase-oysk | DRUG | Recombinant monoclonal antibody, 6 mL vial, via subcutaneous injection per protocol. |
| Loperamide | DRUG | Loperamide : 2 mg orally (PO), twice a day (BID), or 4 mg once a day (QD) during three consecutive days after administration of sacituzumab govitecan, (D2, D3, D4 and D9, D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician). |
| Granulocyte Colony-Stimulating Factor | DRUG | G-CSF : 30 MU subcutaneously (SC) QD during two consecutive days, 48 hours after administration of sacituzumab govitecan (D3, D4 and D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician). |
| Nivolumab | DRUG | Given IV |
| Enfortumab vedotin-ejfv (EV) | DRUG | Intravenous infusion |
| Adaptive Radiotherapy | RADIATION | Concurrently, participants will receive an individualized tailored plan for radiation therapy. |
Inclusion Criteria: 1. ER + PR negative or low positive (≤10% positive cells in IHC), and HER2 negative (i.e., IHC 0 - 1+ or IHC 2+ with FISH negative) breast cancer 2. All patients, independent from gender 3. ≥18 years at diagnosis 4. Histologically confirmed unilateral, primary invasive carcinoma...