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Clinical Trial 20862

Cancer Type: Gastrointestinal Tumor
Study Type: Treatment
NCT#: NCT04336098

Phase: Phase I
Principal Investigator: Mehta, Rutika

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

A Phase 1 Study of SRF617 in Patients with Advanced Solid Tumors

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.

Objective

Primary Objective: Determine the RP2D of SRF617 as monotherapy and in combination therapy in patients with solid tumors Secondary Objectives: Evaluate the safety and tolerability of SRF617 monotherapy and combination therapy Evaluate the PK of SRF617 as monotherapy and combination therapy Evaluate the pharmacodynamics of SRF617 via target occupancy and its relationship to PK Evaluate the preliminary efficacy of SRF617 administered as monotherapy and in combination therapy Evaluate the effect of SRF617 on intratumoral CD39 enzymatic activity (in patients undergoing pretreatment and on-treatment tumor biopsies)

Treatments

Therapies

Chemotherapy (NOS); Immunotherapy

Medications

Albumin-Bound Paclitaxel (); Gemzar (gemcitabine); Pembrolizumab (Keytruda); SRF617 (); gemcitabine ()

Inclusion Criteria

Be > 18 years of age on day of signing the 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). (Exception: patients in combination expansion cohorts please refer to inclusion criteria 12 and 13)

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 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.

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)

Adequate organ function defined per protocol

Prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (aPTT) > Eastern Cooperative Oncology Group performance status of 0 to 1

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

Patients with confirmed advanced PDAC naive to any prior treatment

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

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

For the SRF617+ pembrolizumab safety expansion cohort only:

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

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

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.

Exclusion Criteria

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

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

Major surgery within 4 weeks 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

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

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

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

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

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