| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Castrate-Resistant Prostate Cancer, HR Positive local advanced/metastatic Breast Cancer, Glioblastoma, and Melanoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Advanced Cancer, Prostate Cancer, Breast Cancer, Brain Cancer, and Skin Cancer |
|
| 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 | PT |
| E.1.2 | Classification code | 10018337 |
| E.1.2 | Term | Glioblastoma multiforme |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10076506 |
| E.1.2 | Term | Castration-resistant prostate cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10025650 |
| E.1.2 | Term | Malignant melanoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065147 |
| E.1.2 | Term | Malignant solid tumor |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10055113 |
| E.1.2 | Term | Breast cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the safety and tolerability of ST101 in patients with advanced unresectable and metastatic solid tumors. |
|
| E.2.2 | Secondary objectives of the trial |
To recommend a dose and regimen of ST101 for further development
To determine the PK of ST101 and compare regimens
To assess the preliminary efficacy of ST101 in patients with unresectable cancers of 4 specific tumor types. Efficacy will be assessed by disease control rate (DCR), duration of response (DoR) and progression-free survival (PFS).
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Able and willing to sign ICF and comply with the protocol and the restrictions and assessments therein.
2. Male or female ≥18 years of age.
3. ECOG performance status 0-1.
4. Must have a locally advanced or metastatic inoperable tumor as follows:
a. For the dose escalation/regimen exploration phase: melanoma, carcinoma, or sarcoma
b. For the expansion phase: HRpos LA/MBC, melanoma, GBM, CRPC
5. Agrees to provide a newly obtained biopsy of an accessible lesion (if they can be biopsied based on the investigator's assessment) prior to the start of study treatment, and to repeat biopsy once during study treatment. Tissue obtained for the biopsy must not be previously irradiated (unless progressing following irradiation), but a new or progressing lesion in the radiation field is acceptable. Archived biopsies are acceptable for GBM patients.
6. In the investigator's opinion, the patient may not derive clinical benefit from, or is ineligible for, a particular form of standard therapy on medical grounds, or the patient failed or did not tolerate one or more of other anti-cancer therapies:
a. For the dose escalation/regimen exploration phase:
i. Refractory or intolerant to all available standard-of-care therapies
ii. Up to 3 previous lines of systemic anticancer therapies for metastatic disease are allowed.
b. For the expansion phase:
i. HRpos LA/MBC must have progressed after prior 1-2 hormone-based therapies. Previous treatment with CDK4/6 inhibitor, mTOR inhibitor or chemotherapy is allowed as monotherapy or in combination
ii. Melanoma that has progressed after or on treatment with a CPI and have received 1-2 prior lines of therapy. Patients that have BRAF mutated disease should also have received one line of appropriate targeted therapy
iii. Primary (de novo) GBM that has recurred or progressed (per modified RANO criteria) after 1 standard treatment regimen (surgery, radiotherapy, and temozolomide therapy). Patients that undergo tumor treating fields as an adjuvant to first line therapy are allowed.
iv. CRPC that has progressed after previous treatment with taxanes, abiraterone and enzalutamide unless contraindicated or the patients were intolerant to them.
7. Evaluable disease per RECIST 1.1, modified RANO or PCWG3 with at least one target lesion
8. Disease that progressed on, or is non-responsive to, the previous line of therapy per RECIST 1.1, modified RANO or PCWG3.
9. If not menopausal or surgically sterile, willing to practice at least one of the following highly effective methods of birth control for at least a (partner’s) menstrual cycle before and for four months after ST101 administration: (1) Total abstinence from sexual intercourse with a member of the opposite sex; (2) Sexual intercourse with vasectomized male/sterilized female partner; (3) Combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, parenteral, transvaginal or transdermal) for at least 3 consecutive months prior to investigational product administration; (4) Other acceptable forms of birth control (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicide or cream); (5) Use of an intrauterine contraceptive device.
10. All previous therapy-related AEs should have resolved to grade 1 or baseline value with the exception of alopecia. Levothyroxine is allowed for patients that previously received a CPIs and experienced thyroid dysfunctions.
11. Adequate organ function as indicated by the following laboratory values:
System Laboratory Value
Hematological:
Neutrophils ≥ 1,500/µL
Platelets ≥ 100,000/µL
Hemoglobin ≥ 8 g/dL
Renal:
eGFR (CKD-EPI calculation) ≥ 60 mL/min/1.73m2
Hepatic:
Serum total bilirubin ≤ 1.5 ULN or if >1.5 ULN
Direct bilirubin ≤ ULN
AST/SGOT and ALT/SGPT ≤ 2.5 ULN or ≤ 5 ULN if liver metastases
Coagulation: *
INR ≤ 1.5
aPTT ≤ 1.5 ULN
Chemistry:
Albumin
> 30 g/L
* Unless the patient is receiving therapeutic anticoagulation
12. For prostate cancer patients, the PSA value at screening and baseline should be ≥ 2 µg/L (2 ng/mL).
13. For prostate cancer patients, ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog or orchiectomy (i.e., surgical or medical castration).
a. For patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial.
14. For prostate cancer patients, serum testosterone level < 1.7 nmol/L (50 ng/dL).
15. If receiving bisphosphonate therapy for bone metastases must have been on stable doses for at least 4 weeks
|
|
| E.4 | Principal exclusion criteria |
1. Use of small molecule or tyrosine kinase inhibitor within 2 weeks or 5 half-lives (whichever is shorter) prior to the first dose of study drug; chemotherapy, investigational drug or biological cancer therapy within 3 weeks prior to the first dose of study therapy; nitrosourea or radioisotope within 6 weeks prior to first dose.
2. Known hypersensitivity to ST101 or any of its excipients.
3. Baseline QTc > 480 msec using Fredericia’s formula.
4. Symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
5. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no evidence of new or enlarging brain metastases, and are off steroids for at least 14 days prior to first dose of study drug. This criterion does not apply to patients on the GBM cohort.
6. Presence of any other active malignancy requiring systemic therapy other than the disease under study.
7. Active infection with HIV and CD4+ T-cell count <350/μL. Patients not on established ART for at least four weeks and having a detectable HIV viral load.
8. Active infection with hepatitis B (surface antigen); or infection with hepatitis C, defined by a detectable viral load. Testing is not required for eligibility.
9. Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Vitiligo or resolved childhood asthma/atopy are exceptions to this rule. Patients requiring intermittent use of bronchodilators or topical steroids would not be excluded from the study. Patients with hypothyroidism that is stable on hormone replacement will not be excluded from the study.
10. Use of systemic corticosteroids to treat inflammatory or autoimmune symptoms within 15 days or other immunosuppressive drugs within 30 days prior to the start of the study. Inhaled and topical corticosteroids are permitted. Up to 10 mg/day prednisone or equivalent is permitted as replacement therapy for adrenal insufficiency only.
11. Active infection requiring systemic therapy.
12. Active immune thrombocytopenic purpura or other chronic thrombocytopenic condition.
13. Therapeutic anticoagulation that cannot be interrupted for a biopsy or had a thromboembolic event within the last 6 months.
14. History or clinical evidence of any surgical or medical condition which the investigator judges as likely to interfere with the results of the study or pose an additional risk in participating, or makes the patient unlikely to comply with the study related visits and assessments particularly any pre-existing condition that would put the patient at additional risk should they experience an infusion-related reaction, e.g., rapidly progressive or uncontrolled disease involving a major organ system—vascular, cardiac, pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, or an immunodeficiency
15. Unable to comply with the visits and requirements of the protocol due to psychiatric condition or substance abuse. Pregnant or breastfeeding or planning to conceive or father children within the projected duration of the study.
16. Exclusion criteria for GBM cohort
a. Any prior therapy for GBM other than that which is considered SOC for primary GBM, including but not limited to the following:
i. more than one line of adjuvant temozolomide
ii. prior treatment with another investigational drug
iii. prior treatment with bevacizumab (Avastin) or other VEGF inhibitors or VEGF-receptor signaling inhibitors
iv. prior treatment with nitrosoureas
v. prior therapy that included interstitial brachytherapy or Gliadel® Wafers (carmustine implants)
b. Secondary GBM (i.e., GBM that progressed from low-grade diffuse astrocytoma or AA)
c. Tumor with a clinically significant mass effect (> 5 mm midline shift) while on a stable corticosteroid dose
d. Prednisone or equivalent dose of > 10mg per day
e. Known history of allergy to gadolinium contrast agents
f. Brainstem tumors
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Evaluate the safety and tolerability of ST101 in patients with advanced unresectable and metastatic solid tumors
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs: screening, all visits
Recording of IRRs: all visits
Vital signs: screening, all visits
CBC, Serum Chemistry and Hepatic Panel: screening, all visits
Urinalysis: Screening; d8 (cycle 1); d1 (cycle 2+)
Coagulation: Screening; d1, d8, d15 (cycle 1); d1 (cycle 2+)
ECG: screening, d1, d2 (cycle 1); d1 (cycle 2+)
PE: full PE at screening; directed PE all visits (cycle 1), d1 (cycle 2+)
Plasma histamine: d1, d8 (cycle 1, QW dosing); d1 (cycle 1-2 QOW
dosing)
Serum IgE: d1 (cycle 1), d1 (cycle 2)
Concomitant medicines: screening, all visits |
|
| E.5.2 | Secondary end point(s) |
• Recommend a dose and regimen of ST101 for further development
• Determine the PK of ST101 and compare regimens
• Assess preliminary efficacy of ST101 in patients with unresectable cancers of 4 specific tumor types. Efficacy will be assessed by objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS).
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK: all visits (cycle 1 QW dosing); d1, d8 (cycle 2 QW dosing); d1 (cycle
3 QW dosing); Q3 cycles starting at cycle 7 (QW dosing); d1, d15 (cycle
1 QOW dosing); d1 (cycle 2-3 QOW dosing);Q3 cycles starting at cycle 7
(QOW dosing)
Efficacy (CT/bone scan/MRI): screening, every 9 weeks |
|
| 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 | Yes |
| 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 | Yes |
| 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) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | No |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 29 |
| 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 | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 20 |
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