Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Adenocarcinoma

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Paclitaxel

Gemcitabine

Albumin-Bound Paclitaxel

Immunomodulating Agents

Adenosine

Tubulin Modulators

Antimitotic Agents

Antimetabolites

TTX-030 plus nab-paclitaxel and gemcitabine

TTX-030 plus budigalimab plus nab-paclitaxel and gemcitabine

TTX-030, nab-paclitaxel and gemcitabine

TTX-030, budigalimab, nab-paclitaxel and gemcitabine

Nab-Paclitaxel and gemcitabine

Trishula Therapeutics, Inc.

This is a Phase 2, multicenter, open-label, 3-arm, randomized, parallel group study to evaluate the efficacy and safety of TTX-030 with or without budigalimab in combination with chemotherapy (gemcitabine + nab-paclitaxel) in subjects with metastatic PDAC who did not have prior treatment for metastatic disease and are eligible to receive gemcitabine and nab-paclitaxel chemotherapy as SOC.

Phase 2 Study of TTX-030 and Chemotherapy With or Without Budigalimab for 1L mPDAC Patients

An Open-Label Multicenter 3-Arm Randomized Phase 2 Study to Assess the Efficacy and Safety of TTX-030 and Chemotherapy With or Without Budigalimab, Compared to Chemotherapy Alone, for the Treatment of Patients Not Previously Treated for Metastatic Pancreatic Adenocarcinoma

PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first

ORR is defined as the percentage of subjects who achieve best overall response (BOR) of either complete response (CR) or partial response (PR)

DoR will be defined as the time from the first documentation of disease response (CR or PR) until first documentation of progression or death from any cause, whichever comes first.

OS is defined as the time from randomization until death due to any cause.

Type, severity, and frequency of treatment-emergent AEs

AbbVie

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Urinary Bladder Neoplasms

Pembrolizumab

Docetaxel

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

TTX-030 plus budigalimab (selected tumors evaluated in expansion)

TTX-030 plus budigalimab plus nab-paclitaxel + gemcitabine

TTX-030 plus nab-paclitaxel + gemcitabine

TTX-030, budigalimab and mFOLFOX6

TTX-030, budigalimab and docetaxel

TTX-030 and mFOLFOX6

TTX-030 and budigalimab

TTX-030 and pembrolizumab

Budigalimab and mFOLFOX6

This is a phase 1/1b study of TTX-030 in combination therapy, an antibody that inhibits CD39 enzymatic activity, leading to accumulation of pro-inflammatory adenosine triphosphate (ATP) and reduction of immunosuppressive adenosine, which may change the tumor microenvironment and promote anti-tumor immune response.

This trial will study the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of TTX-030 in combination with immunotherapy and/or standard chemotherapies.

TTX-030 in Combination With Immunotherapy and/or Chemotherapy in Subjects With Advanced Cancers

Phase 1/1b Study to Evaluate the Safety and Activity of TTX-030 (Anti-CD39) in Combination With Pembrolizumab or Budigalimab and/or Chemotherapy in Subjects With Advanced Solid Tumors

Number of study subjects experiencing adverse events (AEs), dose-limiting toxicities, and serious adverse events (SAEs). Safety profile will be assessed through laboratory evaluations, vital signs, and physical examinations.

ORR is defined as the proportion of subjects with CR or PR

DoR will be defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.

DCR is defined as the proportion of subjects with CR, PR, or SD

PFS is measured from documentation of progression or death from any cause, whichever occurs first

Serum concentrations of TTX-030 will be tabulated

Stomach Neoplasms

Stomach Cancer

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

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
Phase 2 Study of TTX-030 and Chemotherapy With or Without Budigalimab for 1L mPDAC Patients	NCT06119217	Pancreatic Canc...	TTX-030, nab-pa... TTX-030, budiga... Nab-Paclitaxel ...	18 Years -	Trishula Therapeutics, Inc.
TTX-030 in Combination With Immunotherapy and/or Chemotherapy in Subjects With Advanced Cancers	NCT04306900	Solid Tumor, Ad...	TTX-030, budiga... TTX-030, budiga... TTX-030 and mFO... TTX-030 and bud... TTX-030, budiga... TTX-030 and pem... TTX-030, nab-pa... Budigalimab and...	18 Years - 110 Years	Trishula Therapeutics, Inc.
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.

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