Study of SRF617 in Patients With Advanced Solid Tumors

NCT04336098 | Completed Phase 1 FDA Drug

• 3 other identifiers: SRF617-101KEYNOTE-A62MK-3475-A62
• Study Type: interventional
• Target: 85
• Locations: 2 countries
• Sites: 10

Brief Summary

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

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

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity of SRF617

  Evaluation of dose-limiting toxicity (DLT).

  Assessed during first 28 days of treatment

Secondary Outcomes (9)

• Safety Analysis: Summary of adverse events (AEs) and based on treatment-emergent AEs (TEAEs)

  Up to 24 months

• Pharmacokinetics (PK) of SRF617

  Up to 24 months

• Pharmacodynamics of SRF617

  Up to 24 months

• Objective response rate (ORR)

  Up to 24 months

• Duration of response (DoR)

  Up to 24 months

Study Arms (8)

Monotherapy Dose Escalation

EXPERIMENTAL

The monotherapy dose escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of SRF617 as monotherapy in up to 36 patients with advanced solid tumors.

Drug: SRF617

Monotherapy Tumor Biopsy Expansion

EXPERIMENTAL

The monotherapy tumor biopsy expansion portion of the study will further evaluate the safety and intratumoral pharmacodynamics of SRF617 monotherapy in up to 20 patients at cleared and recommended phase 2 dose levels.

Drug: SRF617

Combination Therapy - SRF617 with Gemcitabine + Albumin-bound Paclitaxel Dose Escalation

EXPERIMENTAL

This portion of the study will evaluate the safety, tolerability, PK, and preliminary efficacy of SRF617 in combination with gemcitabine + albumin-bound paclitaxel in patients with locally advanced or metastatic solid tumors.

Drug: SRF617; Drug: Gemcitabine; Drug: Albumin-Bound Paclitaxel

Combination Therapy - SRF617 with Pembrolizumab Dose Escalation

EXPERIMENTAL

This portion of the study will evaluate the safety, tolerability, PK, and preliminary efficacy of SRF617 in combination with pembrolizumab (Keytruda®) in patients with locally advanced or metastatic solid tumors.

Drug: SRF617; Drug: Pembrolizumab

Combination Therapy - SRF617 with Gemcitabine + Albumin-bound Paclitaxel Dose Expansion

EXPERIMENTAL

Enrollment at the recommended phase 2 combination dose may be expanded to include approximately 10 additional patients with advanced pancreatic ductal adenocarcinoma (PDAC) to further evaluate safety with SRF617 and gemcitabine + albumin-bound paclitaxel combination therapy.

Drug: SRF617; Drug: Gemcitabine; Drug: Albumin-Bound Paclitaxel

Combination Therapy - SRF617 with Pembrolizumab Dose Expansion GC/GEJ

EXPERIMENTAL

Enrollment at the recommended phase 2 combination dose may be expanded to include approximately 28 additional patients with 2 anti-PD-(L) 1 naive HER2 negative gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma to further evaluate safety with SRF617 and pembrolizumab combination therapy.

Drug: SRF617; Drug: Pembrolizumab

SRF617 + Pembrolizumab + Gemcitabine + Albumin-bound Paclitaxel Quadruplet Dose Expansion

EXPERIMENTAL

Enrollment at the recommended phase 2 combination dose established in the combination dose escalation arms (if recommended phase 2 combination doses differ, the lower of the starting 2 doses will be used) may be expanded to include up to approximately 30 additional patients with advanced 1L PDAC.

Drug: SRF617; Drug: Gemcitabine; Drug: Albumin-Bound Paclitaxel; Drug: Pembrolizumab

Combination Therapy - SRF617 with Pembrolizumab Dose Expansion anti-PD-L1 GC/GEJ, PD-L1+ NSCLC

EXPERIMENTAL

Enrollment at the recommended phase 2 combination dose may be expanded to include approximately 29 additional patients with anti-PD-(L) 1 relapsed/refractory PD-L1+ HER2 negative gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma or advanced PD-L1+ NSCLC to further evaluate safety with SRF617 and pembrolizumab combination therapy.

Drug: SRF617; Drug: Pembrolizumab

Interventions

SRF617 DRUG

SRF617 prevents CD39 mediated conversion of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to adenosine monophosphate (AMP) and phosphate, leading to an increase in extracellular ATP and a reduction in adenosine levels within the tumor microenvironment (TME). There is an important role for extracellular ATP and adenosine in cancer maintenance and progression, and maintaining high levels of ATP (and low levels of adenosine) in the TME may have anticancer therapeutic activity.

Combination Therapy - SRF617 with Gemcitabine + Albumin-bound Paclitaxel Dose Escalation; Combination Therapy - SRF617 with Gemcitabine + Albumin-bound Paclitaxel Dose Expansion; Combination Therapy - SRF617 with Pembrolizumab Dose Escalation; Combination Therapy - SRF617 with Pembrolizumab Dose Expansion GC/GEJ; Combination Therapy - SRF617 with Pembrolizumab Dose Expansion anti-PD-L1 GC/GEJ, PD-L1+ NSCLC; Monotherapy Dose Escalation; Monotherapy Tumor Biopsy Expansion; SRF617 + Pembrolizumab + Gemcitabine + Albumin-bound Paclitaxel Quadruplet Dose Expansion

Gemcitabine DRUG

Gemcitabine as an intravenous (IV) infusion

Also known as: Gemzar®

Combination Therapy - SRF617 with Gemcitabine + Albumin-bound Paclitaxel Dose Escalation; Combination Therapy - SRF617 with Gemcitabine + Albumin-bound Paclitaxel Dose Expansion; SRF617 + Pembrolizumab + Gemcitabine + Albumin-bound Paclitaxel Quadruplet Dose Expansion

Albumin-Bound Paclitaxel DRUG

Albumin-bound paclitaxel as an IV infusion

Also known as: Abraxane®

Combination Therapy - SRF617 with Gemcitabine + Albumin-bound Paclitaxel Dose Escalation; Combination Therapy - SRF617 with Gemcitabine + Albumin-bound Paclitaxel Dose Expansion; SRF617 + Pembrolizumab + Gemcitabine + Albumin-bound Paclitaxel Quadruplet Dose Expansion

Pembrolizumab DRUG

Pembrolizumab as an IV infusion .

Also known as: Keytruda®

Combination Therapy - SRF617 with Pembrolizumab Dose Escalation; Combination Therapy - SRF617 with Pembrolizumab Dose Expansion GC/GEJ; Combination Therapy - SRF617 with Pembrolizumab Dose Expansion anti-PD-L1 GC/GEJ, PD-L1+ NSCLC; SRF617 + Pembrolizumab + Gemcitabine + Albumin-bound Paclitaxel Quadruplet Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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: PDAC patients in 1L combination expansion arms.)
• 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 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.
• 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).
• Adequate renal function
• 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)
• Aspartate aminotransferase and alanine aminotransferase \< 2.5 x ULN (\< 5 x ULN if liver metastasis is present)
• 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
• 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 performance status of 0 to 1
• 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:
• Patients with confirmed advanced PDAC naive to any prior systemic treatment
• 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.
• 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

You may not qualify if:

• 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.
• 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
• For patients in the anti-PD-(L) 1 naïve SRF617 + pembrolizumab combination expansion arm only:
• 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
• Prior therapy with anti-PD-1 or anti-PD-L1 agents is not permitted
• 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
• 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

Sponsors & Collaborators

• Coherus Oncology, Inc.: lead
• Surface Oncology: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

City of Hope

Duarte, California, 91010, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

University of Colorado

Aurora, Colorado, 80045-2517, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75251, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

University of Washington

Seattle, Washington, 98109-1023, United States

Location

University Health Network-Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Universite de Montreal - Centre Hospitalier de l'Universite de Montreal (CHUM) - Hopital Notre-Dame

Montreal, Quebec, H2X 0C1, Canada

Location

MeSH Terms

Conditions

Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Lung Neoplasms

Interventions

Gemcitabine; Albumin-Bound Paclitaxel; pembrolizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Alison O'Neill, MD

  Surface Oncology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 7, 2020
• Study Start: March 16, 2020
• Primary Completion: August 25, 2023
• Study Completion: August 25, 2023
• Last Updated: June 4, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (8)