Study of SRF617 in Patients With Advanced Solid Tumors

• Status: Recruiting
• Trial end date: 2022-11-30
• Target enrollment: 0
• Participant gender: All

Summary

A Phase 1, first-in-human, SRF617 monotherapy and combination therapy, dose escalation, safety, and tumor biopsy expansion study of SRF617, an antibody that inhibits CD39 activity, in patients with advanced solid tumors. Inhibition of CD39 activity may improve the ability to mount an immune response against tumor cells.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Surface Oncology
• Treatments: Adenosine; Albumin-Bound Paclitaxel; Gemcitabine; Paclitaxel; Pembrolizumab

Criteria

Abbreviated Inclusion Criteria:

1. Be ≥ 18 years of age on day of signing the informed consent

2. 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). (Exception: patients in combination expansion cohorts please refer to inclusion criteria 12 and 13)

3. Histological or cytological evidence of advanced, relapsed, or refractory solid tumor cancer that is not a candidate for curative therapy

4. For all patients in the combination expansion cohorts, have at least one lesion that is measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by local site Investigator/radiology. The measurable lesion must be outside of a radiation field if the participant received prior radiation. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

5. 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)

6. Adequate renal function, defined as serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula

7. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤ 3 x 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)

8. Aspartate aminotransferase and alanine aminotransferase < 2.5 x ULN (< 5 x ULN if liver metastasis is present)

9. Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 75 x 109/L. Blood cell transfusion to meet enrollment criteria is not allowed

10. 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

11. Eastern Cooperative Oncology Group performance status of 0 to 1

12. For the SRF617 + gemcitabine + albumin-bound paclitaxel safety expansion cohort only:

1. Patients with confirmed advanced PDAC naive to any prior treatment

2. Prior neoadjuvant therapy for PDAC is permitted if neoadjuvant therapy was completed at least 6 months prior to study enrollment

3. Patients initially diagnosed with locally advanced PDAC who have undergone chemotherapy then resection and had no evidence of disease are eligible if relapse or metastatic disease has occurred and if the last dose of chemotherapy was received more than 6 months before study entry

13. For the SRF617+ pembrolizumab safety expansion cohort only:

1. Patients with Stage IV unresectable locally advanced or metastatic HER2 GEJ who have received a maximum of one prior line of anticancer therapy

2. Patients must be anti PD(L)-1 treatment naïve

14. 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.

Abbreviated Exclusion Criteria:

1. Previously received an anti-CD39 antibody or anti-CD39 targeted therapy

2. History of Grade 3 allergic or anaphylactic reaction to any monoclonal antibody therapy (mAb), or any excipient in the study drugs

3. Major surgery within 4 weeks before Screening

4. 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

5. 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, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137) due to a Grade 3 or higher immune-related AE

6. For patients in the SRF617 + pembrolizumab combination cohort only, prior therapy with anti-PD-1 or anti-PD-L1 agents is not permitted

7. Received prior systemic anti-cancer therapy including investigational agents within 4 weeks before the first dose of study drug Note: For the SRF617+ gemcitabine+ albumin-bound paclitaxel safety expansion cohort only, prior systemic anticancer therapy (except for neoadjuvant therapy) is not permitted

8. 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

9. 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.

10. Has received radiation therapy to the lung that is >30Gy within 6 months of the first dose of study treatment

11. Current pneumonitis or history of (non-infectious) pneumonitis requiring steroids