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

NCT04096638 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: SBP-11285-ONC-101
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Melanoma; Head and Neck Squamous Cell Carcinoma; Solid Tumor

Outcome Measures

Primary Outcomes (7)

• Part 1: Observation of DLT

  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.

  Cycle 1 (4 weeks)

• Part 1: Determination of the MTD

  The maximum tolerated dose (MTD) will be defined as the highest dose level below the maximum administered dose that has confirmed less than 2 out of 6 subjects with DLT. At least 6 subjects evaluable for the safety endpoint must be entered at this dose level before it may be confirmed as the MTD.

  Cycle 1 (4 Weeks)

• Part 1: Determination of the RP2D

  The recommended phase 2 dose (RP2D) will be based on a consideration of the totality of data including but not limited to safety data (including DLTs), PK, PD and preliminary efficacy, as available after completion of Part 1

  8 weeks to 12 months

• Part 1: Incidence of Adverse Events [Safety and Tolerability]

  Incidence of adverse events of SB 11285 as a monotherapy and in combination with atezolizumab when administered as an IV infusion, as determined by patient reporting, clinical laboratory test changes from baseline (hematology, serum chemistry, coagulation, urinalysis, pregnancy, thyroid panel), and clinically significant changes in physical examination data (vital signs and ECG)

  4 weeks to 12 months

• Part 2: Preliminary antitumor activity of SB 11285 in combination with atezolizumab

  Preliminary antitumor activity of SB 11285 in combination with atezolizumab in patients with solid tumors, will be evaluated in terms of objective response rate as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and and by iRECIST

  28 Days to 12 months

• Part 2: Confirmation of recommended RP2D and schedule of SB 11285 in combination with atezolizumab

  Confirmation of the recommended phase 2 dosage (RP2D) and dosing interval will be based on consideration of the totality of available data, including safety, PK, PD, and preliminary efficacy, as available.

  4 weeks to 12 months

• Part 2: Incidence of adverse events [Safety and Tolerability]

  Incidence of adverse events of SB 11285 in combination with atezolizumab when administered as an IV infusion, as determined by patient reporting, clinical laboratory test changes from base line (hematology, serum chemistry, coagulation, urinalysis, pregnancy, thyroid panel), and clinically significant changes in physical examination data (vital signs and ECG)

  4 Weeks to 12 months

Secondary Outcomes (11)

• Part 1 and 2: Cmax (Plasma of SB 11285)

  up to 12 months

• Part 1 and 2: Time to Cmax (Plasma of SB 11285 )

  up to 12 months

• Part 1 and 2: AUC (Plasma of SB 11285 )

  up to 12 months

• Part 1 and 2: Cmax (Plasma of SB 11312)

  up to 12 months

• Part 1 and 2: Time to Cmax (Plasma of SB 11312)

  up to 12 months

Study Arms (5)

Part 1a: Monotherapy Dose Escalation

EXPERIMENTAL

SB 11285 weekly on Days 1, 8, 15 and 22 on repeated 28-day cycles in escalating doses

Drug: SB 11285

Part 1b: PD-L1 Combination Dose Escalation

EXPERIMENTAL

SB 11285 weekly on Days 1, 8, 15 and 22 on repeated 28-day cycles in escalating doses plus 1680mg every 4 weeks (Q4W) atezolizumab

Drug: SB 11285; Drug: Atezolizumab

Part 2: Combination Expansion Cohorts at RP2D (Cohort A)

EXPERIMENTAL

Cohort A: Patients with Melanoma After determination of maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in SB 11285 plus atezolizumab combination the Part 2 with expansion cohorts will commence to further evaluate the RP2D.

Drug: SB 11285; Drug: Atezolizumab

Part 2: Combination Expansion Cohorts at RP2D (Cohort B)

EXPERIMENTAL

Cohort B: Patients with HNSCC After determination of maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in SB 11285 plus atezolizumab combination the Part 2 with expansion cohorts will commence to further evaluate the RP2D.

Drug: SB 11285; Drug: Atezolizumab

Part 2: Combination Expansion Cohorts at RP2D (Cohort C)

EXPERIMENTAL

Cohort 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 atezolizumab combination the Part 2 with expansion cohorts will commence to further evaluate the RP2D.

Drug: SB 11285; Drug: Atezolizumab

Interventions

SB 11285 DRUG

SB 11285 2mg lyophilized powder for IV infusion

Part 1a: Monotherapy Dose Escalation; Part 1b: PD-L1 Combination Dose Escalation; Part 2: Combination Expansion Cohorts at RP2D (Cohort A); Part 2: Combination Expansion Cohorts at RP2D (Cohort B); Part 2: Combination Expansion Cohorts at RP2D (Cohort C)

Atezolizumab DRUG

1680 mg every 4 weeks

Also known as: Tecentriq

Part 1b: PD-L1 Combination Dose Escalation; Part 2: Combination Expansion Cohorts at RP2D (Cohort A); Part 2: Combination Expansion Cohorts at RP2D (Cohort B); Part 2: Combination Expansion Cohorts at RP2D (Cohort C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is at least ≥18 years of age (male or female).
• 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/PD-L1 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)
• Disease characteristics and prior treatments for patients in Part 2:
• 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.
• 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
• An Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Estimated life expectancy ≥3 months
• Measurable disease according to RECIST criteria v 1.1
• 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).
• All women of childbearing potential must have a negative pregnancy test at Screening, prior to study drug administration
• 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)

You may not qualify if:

• Women who are pregnant or lactating or expecting to conceive a child within the projected duration of the study
• 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).
• 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).
• Use of concomitant medications known to moderately or severly prolong QT interval.
• Patients with active or ongoing infection requiring systemic IV antibiotic therapy. Patients with active or ongoing Epstein-Barr virus, hepatitis B virus, or hepatitis C virus or with known human immunodeficiency virus (HIV) infection, tuberculosis, or other infections within 4 weeks.
• 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
• 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
• 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
• Patients with a history of or active pneumonitis Grade ≥ 2 (from any etiology).
• Patients who have discontinued prior immunotherapy due to immune-related adverse reaction(s)
• 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
• Patients who have undergone major surgery within the last 4 weeks
• 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
• 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.
• Patient- Prior treatment with the following agents:

Sponsors & Collaborators

• invoX Pharma Limited: lead

Study Sites (2)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Melanoma; Squamous Cell Carcinoma of Head and Neck

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms

Study Officials

• Naomi Laing

  Vice-President of Clinical Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: September 20, 2019
• Study Start: September 23, 2019
• Primary Completion: July 16, 2024
• Study Completion: July 16, 2024
• Last Updated: October 31, 2024

Record last verified: 2024-03

Locations

US (2)