Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Stomach Neoplasms

Lung Neoplasms

Pancreatic Cancer

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Gemcitabine

Pembrolizumab

Paclitaxel

Albumin-Bound Paclitaxel

Immunomodulating Agents

Adenosine

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

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.

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.

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.

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.

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.

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.

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.

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.

SRF617

Gemcitabine as an intravenous (IV) infusion

Albumin-bound paclitaxel as an IV infusion

Alison O'Neill, MD

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

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).

Study of SRF617 in Patients With Advanced Solid Tumors

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

Evaluation of dose-limiting toxicity (DLT).

Safety and tolerability of SRF617 monotherapy and combination therapy will be assessed by summarizing adverse events (AEs) and will be based on treatment-emergent AEs (TEAEs). A TEAE is an AE that emerges or worsens in the period from the first dose of study drug to 30 days after the last dose of study drug assessed by per CTCAE version 5.0 or higher.

Serum concentrations of SRF617 will be collected and analyzed to evaluate the PK of SRF617.

Pharmacodynamics of SRF617 will be evaluated via serum target occupancy.

ORR will be estimated by the percentage of patients achieving a best overall response of CR or PR per iRECIST.

DoR is defined as the time from the first documented response (CR or PR) to documented disease progression as determined by applicable disease criteria, or documented death due to any cause, whichever occurs first.

DCR is defined as the percentage of patients with CR, partial PR, or stable disease lasting a minimum of 12 weeks.

PFS is defined as the time from the first treatment on study with study drug to documented disease progression as determined by applicable disease criteria or death.

Landmark PFS is defined as the percentage of patients who have not developed PFS events (ie, death or documented disease progression as determined by applicable disease criteria) at 6 months, 1 year, 1.5 years, and 2 years.

Levels of intratumoral CD39 enzymatic activity will be evaluated in patients receiving pretreatment and on-treatment tumor biopsies via an in situ ATPase histochemistry assay.

Merck Sharp & Dohme LLC

Surface Oncology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antibodies

Antibodies, Monoclonal

Immunoglobulins

All patients will receive SRF617 administered in combination with etrumadenant (AB928) and zimberelimab (AB122).

SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39.

Etrumadenant is an A2aR and A2bR antagonist.

etrumadenant

Zimberelimab is a fully human anti-PD-1 monoclonal antibody.

zimberelimab

Vienna Reichert, PhD

This trial will look at the safety and preliminary efficacy of SRF617 in combination with etrumadenant and zimberelimab in patients with metastatic castration-resistant prostate cancer (mCRPC).

This is a phase 2, open-label, safety and preliminary efficacy trial in patients with mCRPC using the combination of SRF617, etrumadenant (AB928), and zimberelimab (AB122).

Study of SRF617 With AB928 (Etrumadenant) and AB122 (Zimberelimab) in Patients With Metastatic Castration Resistant Prostate Cancer

A Phase 2 Trial of SRF617 in Combination With AB928 (Etrumadenant) and AB122 (Zimberelimab) in Patients With Metastatic Castration-Resistant Prostate Cancer

Response was defined as Prostate-Specific Antigen (PSA) decline of ≥ 50% (PSA50) and/or radiographic objective response of Complete Response (CR) or Partial Response (PR) per Prostate Cancer Working Group 3 (PCWG3) Criteria. The number of participants with response shows participants with any one or combination of these response types.

* CR: Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \< 10 millimeters (mm) in short axis
* PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum of diameters

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious Adverse Events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

The number of participants achieving CR or PR by PCWG3 criteria is reported:

* CR: Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \< 10 millimeters (mm) in short axis
* PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum of diameters
* Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions from the smallest value on trial (including Baseline, if that is the smallest). The sum of diameters must also demonstrate an absolute increase of at least 5 mm. Or, the appearance of one or more lesions
* Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD

DOR was defined as the time from first documented response (PSA50 and/or CR/PR) to documented disease progression as determined by applicable disease criteria, or documented death due to any cause, whichever occured first.

DCR was defined as the percentage of participants with CR, PR, or SD lasting a minimum of 12 weeks by PCWG3 or PSA50 criteria.

PSA50 response is defined as a confirmed PSA decrease from Baseline of 50% or more based on 2 consecutive assessments measured 3 to 4 weeks apart.

PSA30 response is defined as a confirmed PSA decrease from Baseline of 30% or more based on 2 consecutive assessments measured 3 to 4 weeks apart.

Landmark PFS was defined as the percentage of participants who have not developed PFS events of death or documented disease progression as determined by applicable disease criteria.

Number of participants with SSEs per PCWG3 criteria, defined as symptomatic fracture, radiation or surgery to bone, or spinal cord compression, is reported.

Arcus Biosciences, Inc.

Coherus Biosciences, Inc.

The Safety Analysis Set included all participants who received any amount of study drug. Also included is 1 participant who discontinued due to an adverse event prior receiving study drug.

SRF617 was administered in combination with etrumadenant and zimberelimab in 28-day cycles according to the following dosing schedule:

* SRF617 1400 mg IV every q2 weeks on Days 1 and 15
* Etrumadenant 150 mg orally daily
* Zimberelimab 480 mg IV q4 weeks on Day 1

SRF617 + Etrumadenant + Zimberelimab

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The Safety Analysis Set included all participants who received any amount of study drug

This study was originally intended to be conducted in 2 stages (1 and 2); however, a strategic decision was made to terminate the study during Stage 1.

Hillary O'Kelly, Executive Director, Clinical Operations

The Response-Evaluable Analysis Set is defined as all participants at Baseline who received study drug and had at least 1 post-Baseline response assessment or who discontinued the treatment phase because of radiographic or symptomatic disease progression (including death caused by disease progression) within 6 weeks (+ 2 week window) of the first dose of study drug.

Number of Participants With Response

Number of Participants With Adverse Events (AEs)

Analysis was not performed as data were not collected for this outcome measure due to early study termination

Number of Participants With Response Per PCWG3 Criteria

Duration of Response (DOR)

Disease Control Rate (DCR)

SRF617 was administered in combination with etrumadenant and zimberelimab in 28-day cycles according to the following dosing schedule:

* SRF617 1400 mg IV every q2 weeks on Days 1 and 15
* Etrumadenant 150 mg orally daily
* Zimberelimab 480 mg IV q4 weeks on Day 1b.

Number of Participants With PSA50 Response

Number of Participants With PSA Decline of ≥ 30% (PSA30) Response

Time to PSA Progression

Radiographic Progression Free Survival (PFS)

Landmark PFS Rate

Participants received SRF617 administered in combination with etrumadenant and zimberelimab.

Maximum Observed Serum Concentration of SRF617 (Cmax)

Minimum Observed Serum Concentration of SRF617 Prior to Administration of Subsequent Dose (Cmin)

Number of Participants With Antidrug Antibodies (ADAs)

Number of Participants With Symptomatic Skeletal Events (SSEs)

SRF617 was administered in combination with etrumadenant and zimberelimab in 28-day cycles according to the following dosing schedule:

* SRF617 1400 milligrams (mg) intravenously (IV) every 2 weeks (q2) on Days 1 and 15
* Etrumadenant 150 mg orally daily
* Zimberelimab 480 mg IV every 4 weeks (q4) on Day 1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of SRF617 in Patients With Advanced Solid Tumors	NCT04336098	Advanced Solid ...	SRF617 Gemcitabine Albumin-Bound P... Pembrolizumab	18 Years -	Surface Oncology
Study of SRF617 With AB928 (Etrumadenant) and AB122 (Zimberelimab) in Patients With Metastatic Castration Resistant Prostate Cancer	NCT05177770	Metastatic Cast... Prostate Cancer	SRF617 etrumadenant zimberelimab	18 Years -	Coherus Biosciences, Inc.
Study of SRF617 With AB928 (Etrumadenant) and AB122 (Zimberelimab) in Patients With Metastatic Castration Resistant Prostate Cancer	NCT05177770	Metastatic Cast... Prostate Cancer	SRF617 etrumadenant zimberelimab	18 Years -	Coherus Biosciences, Inc.

Spots Global Cancer Trial Database for srf617

Every month we try and update this database with for srf617 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for srf617

Every month we try and update this database with for srf617 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for srf617 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.