Clinical trial NCT04336098: Study of SRF617 in Patients With Advanced Solid Tumors
Official title: A Phase 1 Study of SRF617 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: metastatic solid tumors
advanced solid tumors
Phase 1
SRF617
CD39
safety
efficacy
immunotherapy
adenosine pathway
cancer
immuno-oncology
pancreatic cancer
gastric cancer
pembrolizumab
Keytruda®
gemcitabine
albumin-bound paclitaxel
Abraxane®
nab-paclitaxel
gastroesophageal junction adenocarcinoma
GEJ
PD-1
NSCLC
lung cancer
Lead sponsor: Coherus Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Surface Oncology
name: Merck Sharp & Dohme LLC
First posted: 2020-04-07
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 1, first-in-human, monotherapy and combination dose escalation and expansion study of SRF617.

Detailed description: A Phase 1, open-label, first-in-human, study of SRF617, consisting of a monotherapy dose escalation, a monotherapy tumor biopsy expansion, combination dose escalations, and combination safety and efficacy expansions that will enroll patients with advanced solid tumors. The monotherapy dose escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of SRF617 as monotherapy in patients with advanced solid tumors. The monotherapy tumor biopsy expansion portion of the study will further evaluate the safety and intratumoral pharmacodynamics of SRF617 monotherapy. The combination therapy dose escalation portion of the study will evaluate the safety, tolerability, PK, and preliminary efficacy of SRF617 in combination with gemcitabine + albumin-bound paclitaxel, or SRF617 in combination with pembrolizumab, in patients with locally advanced or metastatic solid tumors. Once the SRF617 combination recommended Phase 2 doses are established, additional patients with select solid tumors may be enrolled in the respective combination expansion arm of the study. An additional quadruplet combination will also be explored in patients with advanced first line (1L) PDAC (i.e., SRF617 + pembrolizumab + gemcitabine + albumin-bound paclitaxel).

Eligibility 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: PDAC patients in 1L combination expansion arms.)
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 arms, have at least 1 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 arm only).
6. Adequate renal function
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 expansion arm and SRF617 + pembrolizumab + gemcitabine + albumin-bound paclitaxel quadruplet expansion arm enrolling patients with 1L PDAC only:

    1. Patients with confirmed advanced PDAC naive to any prior systemic treatment
    2. Prior neoadjuvant or adjuvant therapy for PDAC is permitted if neoadjuvant or adjuvant therapy was completed at least 6 months prior to study enrollment. Prior pembrolizumab treatment is not allowed if patient is enrolling in the quadruplet expansion arm.
    3. Patients initially diagnosed with locally advanced PDAC who have undergone chemotherapy then resection and had no evidence of disease are eligible if relapsed or metastatic disease has occurred and if the last dose of chemotherapy was received more than 6 months before study entry
13. For the anti-PD-(L) 1 naïve SRF617+ pembrolizumab combination expansion arm only:

    1. Patients with unresectable locally advanced or metastatic HER2 GEJ who have received a maximum of 2 prior lines of anticancer therapy
    2. Patients must be anti PD(L)-1 treatment naïve
14. For the anti-PD-(L) 1 relapsed/refractor SRF617 + pembrolizumab expansion arm only:

    1. Patients with unresectable locally advanced or metastatic HER2- GC or GEJ adenocarcinoma or unresectable advanced or metastatic NSCLC whose disease is PD-L1+ (defined as CPS ≥ 1 or TPS ≥ 1%).
    2. Must have received at least 1 prior line of systemic anticancer therapy and no more than 4 prior lines of systemic anticancer therapy
    3. Must have anti-PD-(L) 1 relapsed/refractory diseased defined as having progressed on treatment and with anti-PD-(L)1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other immune checkpoint inhibitors or other therapies.
15. 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 pembrolizumab combination arms; 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 women of child-bearing potential (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. In combination expansion arms, patients cannot have previously received agents that inhibit CD73, A2AR, or A2BR.
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. For patients in the anti-PD-(L) 1 naïve SRF617 + pembrolizumab combination expansion arm only:

   1. Discontinuation from previous therapy with an 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 immune-related AE
   2. Prior therapy with anti-PD-1 or anti-PD-L1 agents is not permitted
6. Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 21 days 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 21 days after the last dose of the previous investigational agent
7. 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.
8. Has received radiation therapy to the lung that is \>30Gy within 6 months of the first dose of study treatment
9. Current pneumonitis or history of (non-infectious) pneumonitis requiring steroids

Primary outcomes:
measure: Dose Limiting Toxicity of SRF617
timeFrame: Assessed during first 28 days of treatment
Secondary outcomes:
measure: Safety Analysis: Summary of adverse events (AEs) and based on treatment-emergent AEs (TEAEs)
timeFrame: Up to 24 months
measure: Pharmacokinetics (PK) of SRF617
timeFrame: Up to 24 months
measure: Pharmacodynamics of SRF617
timeFrame: Up to 24 months
measure: Objective response rate (ORR)
timeFrame: Up to 24 months
measure: Duration of response (DoR)
timeFrame: Up to 24 months
measure: Disease control rate (DCR)
timeFrame: Up to 24 months
measure: Progression-free survival (PFS)
timeFrame: Up to 24 months
measure: Landmark PFS rate
timeFrame: Up to 24 months
measure: Effect of SRF617 on intratumoral CD39 enzymatic activity
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: Universite de Montreal - Centre Hospitalier de l'Universite de Montreal (CHUM) - Hopital Notre-Dame
state: Quebec
Study officials:
affiliation: Surface Oncology
name: Alison O'Neill, MD
role: STUDY_CHAIR
References: