Clinical Trials /

A Phase 1-2 Study of ST101 in Patients With Advanced Solid Tumors

NCT04478279

Description:

This is an open-label, two-part, phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 administered IV in patients with advanced solid tumors. The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.

Related Conditions:
  • Breast Carcinoma
  • Carcinoma
  • Glioblastoma
  • Malignant Solid Tumor
  • Melanoma
  • Prostate Carcinoma
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1-2 Study of ST101 in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1-2 Dose-escalation and Expansion Study of ST101 in Patients With Advanced Unresectable and Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ST101-101
  • NCT ID: NCT04478279

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
ST101Dose Escalation

Purpose

This is an open-label, two-part, phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 administered IV in patients with advanced solid tumors. The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.

Detailed Description

      Dose escalation / regimen exploration phase During the dose escalation/regimen exploration
      phase, only patients diagnosed with locally advanced or metastatic melanoma, carcinoma or
      sarcoma of any tumor type who are refractory or intolerant to all available therapies that
      would impact survival will be enrolled.

      ST101 will be administered intravenously (IV), initially once per week. The dose escalation
      cohorts will be recruited using a standard 3+3 design. At each new dosing cohort, there will
      be a 1-week observation period after dosing the first patient in order to assess safety prior
      to dosing the remainder of the patients in that cohort. The dose cohorts will be 0.5, 1, 2,
      4, 8 and 16 mg/kg with once weekly (QW) dosing in all cohorts except for the highest dose
      level which will be dosed every other week (Q2W).

      The expansion phase consists of 4 specific tumor-type cohorts, which each follow the same
      Simon 2-stage design. Fifteen (15) patients will be enrolled in each cohort and treated with
      the ST101 RP2D. If one or more responses is observed that cohort will be expanded to a total
      of 30 patients to further assess efficacy.

      Responses will be graded using response evaluation criteria in solid tumors (RECIST) 1.1
      (Eisenhauer 2009) for hormonal receptor positive (HRpos) locally advanced/metastatic breast
      cancer (LA/MBC) and melanoma, modified response assessment in neuro-oncology (RANO)
      (Ellingson 2017) for GBM and prostate cancer clinical trials working group 3 (PCWG3) (Scher
      2016) for castration-resistant prostate cancer (CRPC).During the expansion phase, only
      patients diagnosed with the following tumor types will be allowed into this phase of the
      study:

        -  HRpos LA/MBC that has progressed after prior 1-2 hormone-based therapies. Previous
           treatment with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, mammalian target of
           rapamycin (mTOR) inhibitor or chemotherapy is allowed as monotherapy or in combination.

        -  Melanoma that has progressed after/or on treatment with an immune checkpoint inhibitor
           (CPI) and have received 1-2 prior lines of therapy for their advanced/metastatic
           disease. Patients that have BRAF mutated disease should also have received one line of
           appropriate targeted therapy.

        -  Primary (de novo) GBM that has recurred or progressed (per modified RANO criteria) after
           1 standard treatment regimen. Standard therapy is defined as maximal surgical resection,
           radiotherapy, and concomitant temozolomide with radiotherapy or adjuvant chemotherapy
           with temozolomide. Patients that undergo tumor treating fields as an adjuvant to first
           line therapy are allowed.- CRPC that has progressed after previous treatment with
           taxanes, abiraterone and enzalutamide/apalutamide.

      The tumor types in the expansion phase may change based on emerging data from the dose
      escalation phase of this study. Additional mini cohorts of 10 patients may be added to the
      expansion phase based on efficacy signals during the dose escalation phase.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalThis cohort only patients diagnosed with locally advanced or metastatic melanoma, carcinoma or sarcoma of any tumor type who are refractory or intolerant to all available therapies. ST101 will be administered intravenously (IV), initially once per week.
  • ST101
Dose Expansion HR+ BreastExperimentalThis cohort must have progressed after 1-2 hormone based therapies. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.
  • ST101
Dose Expansion MelanomaExperimentalThis cohort must have Melanoma that has progressed after/or on treatment with an immune checkpoint inhibitor (CPI) and have received 1-2 prior lines of therapy for their advanced/metastatic disease. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.
  • ST101
Dose Expansion GBMExperimentalPrimary (de novo) GBM that has recurred or progressed (per modified RANO criteria) after 1 standard treatment regimen. Standard therapy is defined as maximal surgical resection, radiotherapy, and concomitant temozolomide with radiotherapy or adjuvant chemotherapy with temozolomide. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.
  • ST101
Dose Expansion CRPCExperimentalCRPC that has progressed after previous treatment with taxanes, abiraterone and enzalutamide/apalutamide. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.
  • ST101

Eligibility Criteria

        Inclusion Criteria:

          -  Inclusion Criteria

               1. Able and willing to sign informed consent form (ICF) and comply with the protocol
                  and the restrictions and assessments therein.

               2. Male or female ≥18 years of age.

               3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

               4. Must have a locally advanced or metastatic inoperable tumor as follows:

                    1. For the dose escalation/regimen exploration phase: melanoma, carcinoma, or
                       sarcoma

                    2. For the expansion phase: HR positive 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 up to 3 previous lines of
                  systemic anticancer therapies are allowed. Since this is a FIH study, it's
                  important that patients are not refractory to therapeutic intervention due to
                  multiple lines of prior therapies.

                  a. For the expansion phase: i. HRpos LA/MBC must have progressed after prior 1-2
                  hormone-based therapies. Previous treatment with cyclin-dependent kinase 4/6
                  (CDK4/6) inhibitor, mammalian target of rapamycin (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 for their advanced/metastatic disease. 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/apalutamide or that are intolerant to these treatments.

               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 anti-cancer therapy-related adverse events should have resolved to
                  grade 1 or baseline value with the exception of alopecia. Levothyroxine is
                  allowed for patients that previously received a CPI and experienced thyroid
                  dysfunction.

                  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 corrected interval between q and t wave on electrocardiogram (ECG) (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 central nervous system (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 human immunodeficiency virus (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. Testing is not required for eligibility.

               8. Active infection with hepatitis B or 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 or controlled type 1 diabetes 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 vascular-endothelial growth
                  factor (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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-Limiting Toxicity (DLT)
Time Frame:20 months
Safety Issue:
Description:Number of Participants with a Dose-Limiting Toxicity (DLT)

Secondary Outcome Measures

Measure:Area Under the Curve (AUC)
Time Frame:30 Months
Safety Issue:
Description:Area under the plasma concentration time curve of ST101
Measure:Cmax
Time Frame:20 months
Safety Issue:
Description:Peak plasma concentration of ST101
Measure:Terminal Half-Life (t1/2)
Time Frame:20 months
Safety Issue:
Description:Elimination half-life of ST101
Measure:Overall Response
Time Frame:20 months
Safety Issue:
Description:Escalation and Expansion Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Measure:DCR
Time Frame:20 Months
Safety Issue:
Description:Expansion: Disease Control Rate, Assessed According to RECIST v1.1
Measure:Duration of Response
Time Frame:20 months
Safety Issue:
Description:Expansion: Duration of Response, Assessed According to RECIST v1.1
Measure:PFS
Time Frame:20 months
Safety Issue:
Description:Expansion: Progression Free Survival, Assessed According to RECIST v1.1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sapience Therapeutics

Last Updated

July 20, 2020