MC# 20-25 - A Phase I Study of SRF617 in Patients With Advanced Solid Tumors (SRF61-101)
Disease Type(s): Solid Tumor
Drug Classification(s): Targeted Therapy, Monoclonal Antibody
Molecular Target(s): CD39
Mechanism of Action
SRF617 is a fully human antibody that is an enzymatic inhibitor of CD39 which may limit ATP degradation and prevent adenosine accumulation in the tumor microenvironment which is a mechanism of tumor immune evasion.
In this study, the sponsor and investigators want to learn:
- About the safety and tolerability of SRF617 alone or in combination with Pembrolizumab or Gemcitabine and Abraxane.
- How proteins that indicate the status of your disease are affected with use of SRF617
- If SRF617 prevents or delays tumor growth or shrinks existing tumors
- How quickly SRF617 is removed from from the bloodstream
- If research tests can be used in the future to predict who will benefit from SRF617
- Be ≥ 18 years of age on day of signing informed consent
- Experienced disease progression during or after standard therapy or were intolerant of standard therapy, and for whom no appropriate therapies are available (based on the judgment of the Investigator)
- Histological or cytological evidence of advanced, relapsed, or refractory solid tumor cancer that is not a candidate for curative therapy
- For all patients in the combination expansion cohorts, have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by local site Investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Have tumor tissue that is accessible for pretreatment and on-treatment biopsy in the opinion of the Investigator and be willing to undergo pretreatment and on-treatment biopsies per protocol (for patients in the monotherapy tumor biopsy expansion cohort only)
- Washout period from the last dose of previous anticancer therapy (chemotherapy, biologic, or other investigational agent) to the initiation of study drug must be > 5 times the half-life of the agent or > 21 days, whichever is shorter. The washout period for palliative radiotherapy is 7 days.
- Resolution of non–immune-related AEs secondary to prior anticancer therapy (excluding alopecia and peripheral neuropathy) to ≤ Grade 1 per NCI-CTCAE version 5.0 or higher, and complete resolution of immune-related AEs secondary to prior checkpoint inhibitor therapy (patients with clinically stable or nonsignificant immune-related AEs [eg, hypothyroidism, vitiligo] or Grade 2 neuropathy related to prior therapy may be enrolled after discussion with Sponsor)
- Adequate renal function, defined as follows:
- For patients to be treated with SRF617 monotherapy or in combination with pembrolizumab, serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula
- For patients to be treated with SRF617 in combination with gemcitabine and albumin-bound paclitaxel, serum creatinine clearance ≥ 50 mL/min per Cockcroft-Gault formula
- Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) (≤ 3 × ULN if elevated because of Gilbert’s syndrome; patients to be treated with SRF617 in combination with albumin- bound paclitaxel must have total bilirubin ≤ 1.5 × ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN (< 5 × ULN if liver metastasis is present)
- Adequate hematologic function, defined as follows:
- For patients to be treated with SRF617 monotherapy, absolute neutrophil count (ANC) ≥ 1.0 × 109/L, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 75 × 109/L
- For patients to be treated with SRF617 in combination with gemcitabine and albumin-bound paclitaxel or with pembrolizumab, ANC ≥ 1.5 × 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 × 109/L. Blood cell transfusion to meet enrollment criteria is not allowed.
- Prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Ejection fraction ≥ 50% as measured by echocardiogram or multigated acquisition (MUGA) scan at Screening
- For women of childbearing potential (WCBP): negative serum β human chorionic gonadotropin (βhCG) pregnancy test within 1 week before first treatment (WCBP are defined as sexually mature women who have not undergone surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months for women > 55 years of age.)
- Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study treatment period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 30 days after the last dose of SRF617, or 120 days after the last dose of pembrolizumab for patients in the SRF617 + pembrolizumab cohort; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements; however, female patients must still undergo pregnancy testing as described in this section.
- Ability to adhere to the study visit schedule and all protocol requirements
- Institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) signed and dated by patient (or legally acceptable representative if applicable) before any Screening procedures are performed
- Previously received an anti-CD39 antibody or anti-CD39 targeted therapy
- Prior severe adverse drug reaction on the relevant combination agent (gemcitabine, albumin-bound paclitaxel, or pembrolizumab; patients in combination therapy cohorts only)
- Active autoimmune disease or medical conditions requiring chronic steroid (ie, ˃ 10 mg/day prednisone or equivalent) or immunosuppressive (eg, cyclosporine) therapy within 7 days before the first dose of study drug. Note: Topical, intranasal, or inhaled corticosteroids and physiologic replacement for patients with adrenal insufficiency are allowed. Premedication corticosteroids for computed tomography (CT) contrast allergy are allowed. Patients with a history of autoimmune disease may be eligible after discussion with the Medical Monitor.
- History of ≥ Grade 3 allergic or anaphylactic reaction to any monoclonal antibody (mAb) therapy or any excipient in the study drugs
- Major surgery within 4 weeks before Screening
- Symptomatic or untreated brain metastases (including leptomeningeal metastases). Patients previously treated for brain metastases must be at least 4 weeks from completion of radiation treatment with follow-up imaging showing no progression.
- Primary central nervous system malignancy
- History of major thromboembolic event (eg, stroke, myocardial infarction, pulmonary embolism) ≤ 6 months before the first dose of SFR617 (patients with history of deep vein thrombosis [DVT] are permitted if they are on stable anticoagulation treatment for at least 3 months before the first dose of study drug)
- Prior autologous stem cell transplant ≤ 3 months before the first dose of SRF617
- Prior allogeneic hematopoietic cell transplant within 6 months before the first dose of SRF617 or with clinical graft-versus-host disease
- Previous chimeric antigen receptor T-cell (CAR-T)/T-cell receptor (TCR) cellular therapy unless able to confirm non-detectable circulating CAR-T/TCR cells
- Known current or prior infection with HIV, hepatitis B virus, or current infection with hepatitis C virus (HCV) (Patients with a history of HCV infection are eligible for enrollment if they have completed curative antiviral treatment and have an HCV viral load below the limit of quantification.)
- Ongoing, uncontrolled, systemic bacterial, fungal, or viral infections at Screening. Note: Oral antibiotics for a controlled infection are permitted. Patients on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met.
- Administration of a live attenuated vaccine within 6 weeks before the first dose of study drug
- Baseline QT interval corrected (QTc) with Fridericia’s method (QTcF) > 480 milliseconds (ms). Note: This criterion does not apply to patients with a right or left bundle branch block.
- Female patients who are pregnant or breastfeeding
- Another malignancy, other than nonmelanoma skin cancer or carcinoma in situ of the cervix, within 2 years before Screening
- History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within 6 months before Screening
- Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator’s judgment, increase the risk to the patient associated with his or her participation in the study
For patients in the SRF617 + pembrolizumab combination cohort only:
- Discontinuation from previous therapy with an anti–PD-1, anti–PD-L1, or anti-programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137) due to a Grade 3 or higher immune-related AE
- Received prior systemic anti-cancer therapy including investigational agents within 4 weeks before the first dose of study drug
- Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study drug. (Note: Patients who have entered the follow-up phase of an investigational study may participate if it has been at least 4 weeks after the last dose of the previous investigational agent.)
- Received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system disease.
- Has received radiation therapy to the lung that is >30Gy within 6 months of the first dose of study treatment.
- Current pneumonitis or history of (non-infectious) pneumonitis requiring steroids
- Dallas, TX - Mary Crowley Cancer Research - Medical City