IRB Study Number 23-597
Status Recruiting
Institute Taussig Cancer Institute
Description
3.1 Primary Objective(s)
(1) Objective (dose escalation phase): To evaluate the safety and tolerability of GI-102 to define the MTD and/or RP2D
(2) Objective (dose expansion phase): To assess the anti-tumor activity of GI-102
3.2 Secondary Objective(s)
(1) Objective (dose escalation phase): To assess the anti-tumor activity of GI-102
(2) Objective (dose expansion phase): To evaluate the safety and tolerability of GI-102
(3) Objective: To characterize the PK profile of GI-102
(4) Objective: To characterize the anti-tumor activity of GI-102 and to determine the relevance of the biomarkers with treatment benefit
Inclusion Criteria
5.1.1 General Inclusion Criteria for All Patients
Must be able to give written informed consent form. The patient may also provide consent/assent for future biomedical research (FBR); however, the patient may participate in the main trial without participating in FBR
Must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and procedures
Males and females aged ≥ 18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening
Male and female patients:
Contraception and abstinence requirements are intended to prevent exposure of an embryo to the study treatment. Patients must agree to remain abstinent or use highly effective or medically accepted double-barrier contraceptive methods as outlined in Section 6.9.
Note: Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Female patients
Females must be non-pregnant and non-lactating and considered of non-reproductive potential as outlined in Section 6.9.
Women of child-bearing potential (WOCBP; Unless considered of non-reproductive potential) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
To participate in the study, WOCBP must agree to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods (Appendix 11) and must adhere to the contraception requirement (from the day of study medication initiation, or 14 days prior to the first dose of study treatment for oral contraception) throughout the study period up to 180 days after the last dose of study medication.
Male patients
Male patients must be considered of non-reproductive potential as outlined in Section 6.9 or agree to remain abstinent and must adhere to the contraception requirement (from the day of study medication initiation, or 14 days prior to the first dose of study treatment for oral contraception) throughout the study period up to 90 days after the last dose of study medication to participate in the study.
- Adequate cardiovascular function:
a. Left ventricular ejection fraction ≥ 50% (resting heart rate between 45 to 100 bpm), as determined by multiple-gated acquisition scan (MUGA) or transthoracic echocardiography (TTE).
b. New York Heart Association (NYHA) Class ≤ 2
c. Baseline-corrected QT (QTc) interval ≤ 470 msec, based on average of 3 readings
d. Resting systolic blood pressure (BP) ≤ 160 mmHg and diastolic BP ≤ 100 mmHg at screening. BP should be measured after at least 5-minute resting and 3 readings are averaged.
e. Resting heart rate between 45 to 100 bpm.
- Patients with unilateral pleural effusion (indications other than lung cancers (NSCLC, SCLC, etc.) are eligible if they fulfill both of the following:
a. NYHA Class 1
b. Forced expiratory volume 1 (FEV1) and forced vital capacity (FVC) > 70% of predicted value; patients with lung metastases should present with Diffusing capacity of the lungs for carbon monoxide (DLCO) > 60% of predicted value.
- Has adequate organ function as defined in Table 5. Specimens must be collected within 7 days prior to the first dose of study treatment. Adequate organ and marrow function as defined below: (See protocol)
5.1.2 Cancer Related Inclusion Criteria
Histologic or cytologic documentation of locally advanced, recurrent, or metastatic incurable malignancy that has documented disease progression after available standard therapy, as judged by the Investigator, or for whom standard therapy has proven to be ineffective or intolerable or is considered inappropriate, or for whom a clinical trial of an investigational agent is a recognized standard of care.
Have measurable disease by RECIST v1.1, assessed by the investigator. Radiology target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Has recovered to CTCAE Grade ≤ 1 from the AEs related to any previous chemotherapy, radiotherapy, immunotherapy, other prior systemic anticancer therapy, or surgery. Patients with alopecia (any grade) and Grade 2 peripheral neuropathy will be permitted.
Must consent to provide archival tumor tissue collected from prior surgery or biopsy within 6 months of screening, if available from prior surgery or biopsy. Formalin-fixed, paraffine embedded (FFPE) tissue blocks are preferred to slide.
Note: If patients may not consent to provide present archival tumor tissue, Sponsor consultation is required for the eligibility confirmation.
- Patients who consent to fresh tumor biopsies:
Confirmed with at least one tumor lesion with location accessible to safely biopsy per the clinical judgment of the investigator and the patient’s consented willingness to undergo baseline and on-treatment tumor biopsies for PD biomarker analysis. Previously irradiated lesions should not be counted as target lesions unless there is a documented evidence of progression post radiation. Lesions that are intended to be biopsied should not be counted as target lesions.
Patients who consent to serial biopsies and then do not get one or based on (1) inaccessible tumor; (2) biopsy not felt in the patient’s best interest; (3) patient (later) refuses (as is his/her right) will be still permitted to remain on study.
Note: Additional patients in dose escalation phase and all patients enrolled in dose expansion phase must consent to serial tumor biopsies (baseline and on-treatment). If mandatory biopsies cannot be performed as per investigator’s clinical judgement, discussion and agreement between the investigator and Sponsor are required.
- HIV infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:
a. Patients on ART must have a CD4+ T-cell count > 350 cells/mm3 at time of screening
b. Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening
c. Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1)
5.1.3 Additional Inclusion Criteria for each Part
Dose-expansion phase
For RCC, patients with histologically or cytologically confirmed incurable, advanced RCC with component of clear cell histology and/or component of sarcomatoid histology
For melanoma, patients with histologically or cytologically confirmed incurable, advanced melanoma
Exclusion Criteria
5.2.1 General Exclusion Criteria
- Has known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastasis may participate provided they are (1) radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening unless there is pre-study imaging within 12 weeks prior to the first dose of study treatment), (2) clinically stable and (3) without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
Note: For the patients with melanoma and/or lung cancers (NSCLC, SCLC, etc.), if patients have not had the previous brain imaging which indicated no brain lesion was observed within 1 year from the first dose of study treatment, it is strongly recommended to perform the brain imaging at Screening, at the Investigator’s discretion. If for logistical or administrative reasons the brain imaging cannot be performed within the official screening window, Sponsor consultation is required.
Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ≥ 2 weeks before enrolment.
Has an active second malignancy in past 5 years (exceptions are non-melanoma skin cancer, cervical carcinoma in situ, or prostate carcinoma that is in remission under androgen deprivation-therapy for > 2 years, or patients who have a history of malignancy and have been treated with curative intent and the patient is expected to be cured as per Investigator’s assessment). Other exceptions may apply and require discussion between the Investigator and the Sponsor.
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, and known autoimmune diseases or other disease with ongoing fibrosis (such as, scleroderma, pulmonary fibrosis, and emphysema).
Episode of significant cardiovascular/cerebrovascular acute disease within 6 months before study treatment administration, including any of the following: (1) hypertensive crisis/encephalopathy, (2) uncontrolled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg), (3) unstable angina, (4) transient ischemic attack/stroke, (5) congestive heart failure of any NYHA classification (for NYHA classification, refer to inclusion criteria), (6) serious cardiac arrhythmia requiring treatment (exceptions are atrial fibrillation, paroxysmal supraventricular tachycardia), (7) history of thromboembolic events (such as myocardial infarction, stroke or pulmonary embolism).
Has active or a known history of Hepatitis B (defined as Hepatitis B surface antigen [HbsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
Has active tuberculosis or has a known history of active tuberculosis. If there is documented evidence that tuberculosis was completely recovered at least 3 years prior to screening and have no other reasons for exclusion, the patient’s study participation is allowed per investigators’ judgement.
Active or uncontrolled infections, or severe infection within 4 weeks before study treatment administration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
History of chronic liver disease or evidence of hepatic cirrhosis, except patients with liver metastasis.
Dementia or altered mental status that would prohibit informed consent.
Has an active autoimmune disease that has required systemic treatment in past 2 years (e.g., with use of disease modifying agent, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment, and patients with the replacement therapy will not be excluded from participation in this trial.
History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (e.g., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan.
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug.
Is currently participating in or has participated in a study of an investigational product (defined as a treatment for which there is currently no regulatory authority-approved indication) or has used an investigational device within 4 weeks prior to the first dose of study treatment.
Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of previous investigational product or use of investigational device.
- Immunomodulating agents:
a. Last dose with any of the following agents, for example, etanercept, infliximab, tacrolimus, cyclosporine, mycophenolic acid, alefacept, or efalizumab (or similar agents) < 28 days prior to the first dose of study treatment
b. Previous immunotherapies related to mode of action of GI-102 including, but not limited to, any cytokine therapies, particularly IL-2, IL-7, IL-10, IL-15, and their conjugates, interferon alpha (IFN-α), IFN-β, IFN-γ or CD80 containing therapeutics. The use of these agents more than 3 years prior to study treatment may be acceptable after the discussion between the Investigator and the Sponsor
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive medications including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to the first dose of study treatment. Patients with the use of inhaled corticosteroids, intra-articular injection, topical ointment/lotion, gargle steroid or mineralocorticoids (e.g., fludrocortisone) will not be excluded from participation in this trial.
Note: Patients who have received acute and/or low-dose systemic immunosuppressive medications (e.g., a one-time dose of dexamethasone for nausea or chronic use of ≤ 10 mg/day of prednisone or dose-equivalent corticosteroid) may be enrolled in the trial after discussion with and approval by the Medical Monitor
Has had previous systemic anti-cancer therapy including investigational agents within 4 weeks prior to the first dose of study treatment. Patients should have recovered from clinically significant adverse events from their most recent systemic therapy or intervention prior to study enrollment
Radiotherapy within the last 2 weeks prior to the first dose of study treatment, with exception of limited field palliative radiotherapy. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation induced pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
Note: Patients who have received radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study treatment will be excluded from participation in this study
Has received a live, attenuated vaccine within 28 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccine and are permitted; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
Has had major surgery or significant traumatic injury < 28 days prior to the first dose of study treatment (excluding fine needle biopsies) or anticipation of the need for major surgery during study treatment.
Known hypersensitivity to any of the components of the drug products and/or excipients of GI-102.
History of (non-infectious) pneumonitis / interstitial lung disease that required steroids or current pneumonitis / interstitial lung disease.
Severe dyspnea at rest or requiring supplementary oxygen therapy.
Eligibility of patients who require blood transfusion before and after the start of the trial treatment should be discussed by the Sponsor and Investigator.
Has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the trial, interfere with the patient’s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the Investigator.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of study treatment.
HIV-infected patients with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
Has had an allogeneic tissue/solid organ transplant.
5.2.2 Specific Exclusion Criteria
- For patients who received previous cancer immunotherapy (e.g., anti-PD-1/PD-L1 or anti-CTLA-4, etc.):
Patients who discontinued from that treatment due to treatment-associated toxicity or intolerability or have any history of Grade ≥ 3 irAEs attributed to that treatment (with exception of endocrinopathy managed with replacement therapy)
Note: Patients receiving ongoing hormone replacement therapy for endocrine irAEs will not be excluded from the participation in this trial.
