Clinical Trials /

Evaluating Safety and Efficacy of SB 11285 Alone and in Combination With Nivolumab in Patients With Advanced Solid Tumors

NCT04096638

Description:

A Phase 1a/1b, multicenter, open-label, non-randomized, dose-escalation, and cohort expansion study to examine the DLTs, MTD, and RP2D of SB 11285 administered as an IV infusion in patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Evaluating Safety and Efficacy of SB 11285 Alone and in Combination With Nivolumab in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1a/1b Dose-escalation Study of Intravenously Administered SB 11285 Alone and in Combination With Nivolumab in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: SBP-11285-ONC-101
  • NCT ID: NCT04096638

Conditions

  • Melanoma
  • Head and Neck Squamous Cell Carcinoma
  • Solid Tumor

Interventions

DrugSynonymsArms
SB 11285Part 1a: Monotherapy Dose Escalation
NivolumabOpdivoPart 1b: PD-1 Combination Dose Escalation

Purpose

A Phase 1a/1b, multicenter, open-label, non-randomized, dose-escalation, and cohort expansion study to examine the DLTs, MTD, and RP2D of SB 11285 administered as an IV infusion in patients with advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
Part 1a: Monotherapy Dose EscalationExperimentalSB 11285 weekly on Days 1, 8, 15 and 22 on repeated 28-day cycles in escalating doses (0.3-14 SB 11285 µg/Kg)
  • SB 11285
Part 1b: PD-1 Combination Dose EscalationExperimentalSB 11285 weekly on Days 1, 8, 15 and 22 on repeated 28-day cycles in escalating doses (0.3-3.0 SB 11285 µg/Kg) plus 480mg every 4 weeks (Q4W) nivolumab
  • SB 11285
  • Nivolumab
Part 2: Combination Expansion Cohorts at RP2D (Cohort A)ExperimentalCohort A: Patients with Melanoma After determination of maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in SB 11285 plus nivolumab combination the Part 2 with Expansion Cohorts will commence to further evaluate the RP2D.
  • SB 11285
  • Nivolumab
Part 2: Combination Expansion Cohorts at RP2D (Cohort B)ExperimentalCohort B: Patients with HNSCC After determination of maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in SB 11285 plus nivolumab combination the Part 2 with Expansion Cohorts will commence to further evaluate the RP2D.
  • SB 11285
  • Nivolumab
Part 2: Combination Expansion Cohorts at RP2D (Cohort C)ExperimentalCohort C: Patients with tumor types other then Cohort A and B (Naïve or relapsed refractory to anti PD-1/PD-L1) After determination of maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in SB 11285 plus nivolumab combination the Part 2 with Expansion Cohorts will commence to further evaluate the RP2D.
  • SB 11285
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patient is at least ≥18 years of age (male or female).

          2. Disease characteristics for patients in Part 1:

             a. Patient with any histologically or cytologically confirmed solid tumor that is
             locally advanced or metastatic or unresectable tumor and has disease progression after
             treatment with available therapies that are known to confer clinical benefit or who
             are intolerant to treatment.

             Note: Tumor types of primary interest in Part 1 Dose Escalation include tumors which
             are relapsed or refractory after anti PD-1 therapy (include but not limited to
             malignant melanoma, HNSCC, renal cell carcinoma, hepatocellular carcinoma, Merkel cell
             carcinoma, urothelial, non-small cell lung cancer, gastric carcinoma, ovarian
             carcinoma, endometrial, TNBC, cervical cancer, and colorectal carcinoma)

          3. Disease characteristics and prior treatments for patients in Part 2:

               1. Cohort A (Melanoma): Patients with advanced or metastatic melanoma who have
                  progressed following treatment with an anti-PD-1 or anti-PD-L1 antibody. Patients
                  with BRAF mutated melanoma must have previously received BRAF/MEK targeted
                  therapy.

               2. Cohort B (Head and Neck): Patient has anti-PD-1/PD-L1 refractory metastatic or
                  recurrent HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx.
                  Participants may not have a primary tumor site of the nasopharynx (any
                  histology).

             i. Has histologically confirmed Stage III, IVa, or IVb disease per TNM staging,
             American Joint Committee on Cancer (AJCC, 8th edition), with recurrent or persistent
             disease after definitive chemoradiation, deemed unresectable and considered refractory
             to both platinum-based combination chemotherapy and anti-PD-1/PD-L1 antibody therapy
             OR ii. Has histologically confirmed Stage IVc disease per TNM staging, AJCC 8th
             edition, considered refractory to platinum-based combination chemotherapy and
             anti-PD-1/PD-L1 antibody therapy.

             c. Cohort C: Tumor types not in Cohort A and B - Naïve or relapsed refractory to anti
             PD-1/PD-L1

          4. An Eastern Cooperative Oncology Group (ECOG) performance status ≤1

          5. Estimated life expectancy ≥3 months

          6. Measurable disease according to RECIST criteria v 1.1

          7. Patients must have recovered (ie, to NCI CTCAE grade ≤1) from all toxicity associated
             with previous treatments (exception: patients may enter with continuing alopecia
             irrespective of CTCAE grade).

          8. All women of childbearing potential must have a negative pregnancy test at Screening,
             prior to study drug administration

          9. Women of childbearing potential include any female who has experienced menarche and
             who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal
             ligation, or bilateral oophorectomy) or is not postmenopausal. Postmenopausal is
             defined as: (1) Amenorrhea ≥12 consecutive months without another cause and a
             documented serum follicle stimulating hormone (FSH) level >35 mIU/mL; (2) Women with
             irregular menstrual periods and a documented serum FSH level >35 mIU/mL; or (3) Women
             on hormone replacement therapy (HRT)

         10. All patients, male and female, who are not surgically sterilized or postmenopausal as
             defined above, must agree to use dual effective birth control during the study and for
             at least 28 days after the last dose of study medication.

             Highly effective methods of contraception are hormonal contraceptives (oral,
             injectable, patch, intrauterine devices), male partner sterilization, or total
             abstinence from heterosexual intercourse, when this is the preferred and usual
             lifestyle of the patient. Note: The double-barrier method (eg, synthetic condoms,
             diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence
             (such as calendar, symptothermal, post-ovulation), withdrawal (coitus interruptus),
             lactational amenorrhea method, and spermicide only are not acceptable as highly
             effective methods of contraception

         11. Patients has adequate hematologic and organ function, defined as:

               1. ANC ≥1500 mm3

               2. Platelets ≥100,000/mm3

               3. Hemoglobin ≥9 g/dL Note: Patients with Hb 7 to ≤9 g/dL (without bleeding)
                  transfused prior to dosing in order to meet eligibility criteria

               4. Creatinine clearance ≥60 mL/min by Cockcroft-Gault (C-G) equation or estimated
                  glomerular filtration rate (eGFR) ≥ 60 mL/min

               5. Alanine aminotransferase (ALT), aspartate transaminase (AST) ≤3.0× the upper
                  limit of normal (ULN) if no liver involvement or ≤5×ULN with liver involvement

               6. Adequate coagulation: prothrombin time (PT) and an International Normalized Ratio
                  (INR) and activated partial thromboplastin time (aPTT) ≤1.5×ULN

               7. Total bilirubin ≤1.5×ULN (or total serum bilirubin ≤3×ULN for patients with
                  Gilbert's disease)

         12. Patients must be willing and able to provide written informed consent prior to the
             performance of any study-specific procedure

        Exclusion Criteria:

          1. Women who are pregnant or lactating or expecting to conceive a child within the
             projected duration of the study

          2. History or evidence of cardiovascular (CV) risk including any of the following: Recent
             (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or
             clinically significant ECG abnormalities including second degree (Type II) or third
             degree atrioventricular block; Cardiomyopathy, myocardial infarction, acute coronary
             syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or
             bypass grafting within the past 6 months before enrolment; Congestive heart failure
             (Class II, III, or IV) as defined by the New York Heart Association functional
             classification system (NYHA).

          3. Patients with marked Baseline QTc prolongation (QT interval corrected for rate by
             Fridericia's formula [QTcF] ≤470 msec for women and ≤450 msec for men on the ECG
             obtained at Screening by mean of three ECGs).

          4. Use of concomitant medications known to prolong QT interval.

          5. Patients with active, ongoing infection requiring systemic antibiotic therapy or with
             active Epstein-Barr virus, hepatitis B virus, or hepatitis C virus or with known human
             immunodeficiency virus (HIV) infection. Note: HIV testing is not required for
             eligibility, but if performed previously and was positive, the patient is ineligible
             for the study

          6. Clinically significant pulmonary disease, chronic or recurrent renal or urinary tract
             disease, liver disease, endocrine disorder, autoimmune disorder, or neuromuscular,
             musculoskeletal, or mucocutaneous conditions that, in the opinion of the Investigator,
             put the patient at additional risk by participating in the study or otherwise make the
             patient unsuitable for the study

          7. The patient has uncontrolled intercurrent illness including, but not limited to
             uncontrolled infection, including uncontrolled diabetes mellitus or decreased
             pulmonary function, or psychiatric illness/social situations that would limit
             compliance with study

          8. Has an active autoimmune disease that has required systemic treatment in the past 2
             years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive
             drugs) except vitiligo or resolved childhood asthma/atopy. Replacement therapy, such
             as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal
             or pituitary insufficiency, is not considered a form of systemic treatment

          9. Patients with a history of or active drug induced pneumonitis Grade ≥ 2.

         10. Patients who have discontinued prior immunotherapy due to immune-related adverse
             reaction(s)

         11. Is on chronic systemic steroid therapy in excess of replacement doses (prednisone ≤10
             mg/day is acceptable), or on any other form of immunosuppressive medication. Note: The
             use of physiologic replacement doses of corticosteroids may be approved after
             consultation with the Sponsor's Medical Monitor or designee

         12. Patients who have undergone major surgery within the last 4 weeks

         13. Patients with new brain metastasis. Patients with treated (surgically excised or
             irradiated) and stable brain metastases are eligible as long as the treatment was at
             least 4 weeks prior to initiation of study drug and baseline brain CT with contrast or
             MRI within 2 weeks of initiation of study drug is negative for new brain metastases

         14. Active malignant disease other than that being treated in this study. Exceptions:
             malignancies that were treated curatively and have not recurred within the past 2
             years; completely resected basal cell carcinoma and squamous cell carcinoma of the
             skin; and completely resected carcinoma in situ of any type.

         15. Patient- Prior treatment with the following agents:

               1. Stimulator of Interferon Genes (STING) agonist at any time.

               2. Anticancer therapy or investigational therapy within 28 days or 5 half-lives of
                  the drug, whichever is shorter; "Check-point inhibitors", including Programmed
                  death receptor-1 (PD-1), PD-L1 and Cytotoxic T-lymphocyte-associated antigen 4
                  (CTLA-4) inhibitors within 28 days (except part 2 Cohort C);

               3. Prior radiation therapy: permissible if at least 1 non-irradiated measurable
                  lesion is available for assessment according to RECIST version 1.1 or if a
                  solitary measurable lesion was irradiated, objective progression is documented. A
                  wash out of at least 28 days before start of study treatment for radiation of any
                  intended use to the extremities for bone metastases and 28 days for radiation to
                  the chest, brain, or visceral organs is required. Palliative radiation is
                  permissible at any time before or during the study.

         16. Receipt of any live vaccines within 4 weeks prior to the initiation of study drug.

         17. Patients considered by Investigators for any other reason to be unsuitable for the
             study or unable to comply with all study procedures and follow-up examinations.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Observation of DLT
Time Frame:Cycle 1 (4 weeks)
Safety Issue:
Description:Dose-limiting toxicity (DLT) is defined as a clinically significant adverse event or abnormal laboratory value occurring during Cycle 1 (Days 1-28) during both monotherapy and Combination dose-escalation portions of Part 1. Adverse events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Secondary Outcome Measures

Measure:Part 1 and 2: Cmax (Plasma of SB 11285)
Time Frame:up to 12 months
Safety Issue:
Description:To characterize the plasma pharmacokinetics (PK) of SB 11285 following IV administration of SB 11285 as monotherapy and in combination with nivolumab, the PK endpoint maximum plasma concentration (Cmax) will be measured.
Measure:Part 1 and 2: Time to Cmax (Plasma of SB 11285 )
Time Frame:up to 12 months
Safety Issue:
Description:To characterize the plasma pharmacokinetics (PK) of SB 11285 following IV administration of SB 11285 as monotherapy and in combination with nivolumab, the PK endpoints time to maximum plasma concentration (Cmax) will be measured.
Measure:Part 1 and 2: AUC (Plasma of SB 11285 )
Time Frame:up to 12 months
Safety Issue:
Description:To characterize the plasma pharmacokinetics (PK) of SB 11285 following IV administration of SB 11285 as monotherapy and in combination with nivolumab, the PK endpoint area under the concentration-time curve will be measured.
Measure:Part 1 and 2: Cmax (Plasma of SB 11312)
Time Frame:up to 12 months
Safety Issue:
Description:To characterize the plasma pharmacokinetics (PK) of SB 11312 following IV administration of SB 11285 as monotherapy and in combination with nivolumab, the PK endpoint maximum plasma concentration (Cmax) will be measured.
Measure:Part 1 and 2: Time to Cmax (Plasma of SB 11312)
Time Frame:up to 12 months
Safety Issue:
Description:To characterize the plasma pharmacokinetics (PK) of SB 11312 following IV administration of SB 11285 as monotherapy and in combination with nivolumab, the PK endpoints time to maximum plasma concentration (Cmax) will be measured.
Measure:Part 1 and 2: AUC (Plasma of SB 11312)
Time Frame:up to 12 months
Safety Issue:
Description:To characterize the plasma pharmacokinetics (PK) of SB 11312 following IV administration of SB 11285 as monotherapy and in combination with nivolumab, the PK endpoint area under the concentration-time curve will be measured.
Measure:Part 1 and 2: Plasma of SB 11312
Time Frame:up to 12 months
Safety Issue:
Description:To characterize the plasma pharmacokinetics (PK) of SB 11312 following IV administration of SB 11285 as monotherapy and in combination with nivolumab, the PK endpoint area under the concentration-time curve will be measured.
Measure:Part 1: Objective response rate (ORR)
Time Frame:4 weeks to 12 months
Safety Issue:
Description:Objective response rate (ORR) assessed by RECIST v 1.1 for patients in Part 1 only
Measure:Part 1 and 2: Duration of response (DOR)
Time Frame:4 weeks to 12 months
Safety Issue:
Description:Duration of response (DOR) assessed by RECIST v 1.1 and by iRECIST (Part 1 and 2)
Measure:Part 1 and 2: Progression-free survival (PFS)
Time Frame:4 weeks to 12 months
Safety Issue:
Description:Progression-free survival (PFS) assessed by RECIST v 1.1 and by iRECIST
Measure:Part 1 and 2: Overall survival (OS)
Time Frame:up to 39 months
Safety Issue:
Description:Overall survival (OS) is defined as time from date of first study treatment to death due to any cause. The Kaplan-Meier method will be used to estimate the median OS.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Spring Bank Pharmaceuticals, Inc.

Last Updated