Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Immunomodulating Agents

Atezolizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint Inhibitors

Participants will receive treatment until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Participants will receive treatment until unacceptable toxicity or loss of clinical benefit as confirmed by disease progression per RECIST V1.1 or lack of continued benefit as determined by the investigator.

Regorafenib will be administered orally on Days 1-21 of each 28-day cycle.

Regorafenib

Atezolizumab will be administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of 21-day cycles, with the exception of the Atezolizumab + Selicrelumab + Bevacizumab, Atezolizumab + Idasanutlin, Atezolizumab + Regorafenib and Atezolizumab + Regorafenib + AB928 arms where the Atezolizumab will be administered by IV infusion every 2 weeks (Q2W) on Days 1 and 15 of each 28-day cycle.

Imprime PGG will be administered by IV infusion weekly on Days 1, 8, and 15 of each 21-day cycle.

Imprime PGG

Bevacizumab will be administered by IV infusion on Day 1 of each 21-day cycle for the Atezolizumab + Imprime PGG + Bevacizumab arm, and on Day 1 and Day 15 of each 28-day cycle for the Atezolizumab + Selicrelumab + Bevacizumab arm.

Isatuximab will be administered on Day 1, 8 and 15 of cycle 1 and on day 1 of all subsequent cycles. Cycles will be 21 days long.

Isatuximab

Selicrelumab will be administered by subcutaneous (SC) injection on Day 1 of cycles 1-4 and every third cycle thereafter. Cycles will be 28 days long.

Selicrelumab

Idasanutlin will be administered orally on Days 1-5 of each 28-day cycle.

Idasanutlin

AB928 will be administered orally once daily on Days 1-28 of each 28-day cycle.

AB928

LOAd703 will be administered by intratumoral injection on Day 1 of each 21-day cycle.

LOAd703

Clinical Trials

A phase Ib/II, open-label, multicenter, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with metastatic colorectal cancer (mCRC) that became refractory to first- and second-line standard therapies. Eligible patients will be assigned to one of several treatment arms.

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)

The best confirmed overall response rate (ORR) is defined as the percentage of participants with a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to RECIST v1.1. Participants could be classified as "Stable Disease" if the assessment was at least 6 weeks from randomization. Participants were classified as Missing if no post-baseline response assessments were available. Participants were classified as Not Evaluable if all post-baseline response assessments were unevaluable. The differences in ORR between the experimental arms and the corresponding control arm were calculated, along with 95% confidence intervals (CIs), using normal approximation of the binomial distribution. The 95% CIs for ORRs were constructed using the Clopper-Pearson method. The 95% CIs for the difference in rates were constructed using the Wald method with continuity correction.

Progression-free survival (PFS) after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), was determined by the investigator according to RECIST v1.1. For participants who did not have documented disease progression or death, PFS was censored at the day of the last tumor assessment. The Kaplan-Meier method was used to estimate the median for PFS with 95% confidence intervals (CIs) constructed through use of the Brookmeyer and Crowley method.

Overall survival (OS) is defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The Kaplan-Meier method was used to estimate the median for OS with 95% confidence intervals (CIs) constructed through use of the Brookmeyer and Crowley method.

Overall survival (OS) is defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. OS is shown as the percentage of participants who were event-free at the landmark timepoints of 3, 6, 12, and 18 months.

Duration of response is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause.

Disease control rate is defined as the percentage of participants with stable disease for ≥12 weeks or a complete or partial response, as determined by the investigator according to RECIST v1.1.

The incidence, nature, and severity of adverse events (AEs) are reported, with severity determined according to NCI CTCAE v4.0. All AEs were reported until 30 days after the last study dose or until start of new systemic anti-cancer therapy. Serious AEs and AEs of special interest were reported until 135 days (or 180 days for the Atezolizumab + LOAd703 arm only) after the last dose of study treatment.

Hoffmann-La Roche

All-Cause Mortality is reported in the all-enrolled patients population. Adverse events (AEs) are reported in the safety population, defined as all those who received ≥1 dose of study treatment. One participant in the Regorafenib arm died before receiving study dose. All AEs were reported until 30 days after the last study dose or until the start of new systemic anti-cancer therapy. Serious AEs and AEs of special interest are reported until up to 180 days after last study dose.

Regorafenib (Control)

Atezolizumab + Imprime PGG + Bevacizumab

Atezolizumab + Isatuximab

Atezolizumab + Selicrelumab + Bevacizumab

Atezolizumab + Idasanutlin

Atezolizumab + Regorafenib

Atezolizumab + Regorafenib + AB928

Atezolizumab + LOAd703

Total

Age (year)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

ECOG performance status scale. 0 - Fully active; able to carry on all predisease performance without restriction

1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature

ECOG score

Number of Metastatic Sites at Enrollment

All participants who were randomized in the study, regardless of whether they actually received any study treatment.

This study is not designed to make explicit power and Type I error considerations for a hypothesis test. Instead, this study is designed to obtain preliminary efficacy, safety, and PK data. No formal statistical hypothesis testing was performed in this study. Due to the limited sample size, the results need to be interpreted with caution. For the Atezo+Idasa and Atezo+LOAd703 groups, no meaningful conclusion could be drawn because these experimental arms have been terminated prematurely.

Medical Communications

Responders (CR + PR)

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Progressive Disease (PD)

Not Evaluable

Missing

The efficacy evaluable population included all patients who received at least one dose of each drug for their assigned treatment regimen.

Best Confirmed Overall Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Progression-Free Survival (PFS) as Determined by Investigator According to RECIST v1.1

Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Isatuximab vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Idasanutlin vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Regorafenib vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) Hazard Ratio for OS

Atezolizumab + LOAd703 vs. Regorafenib (Control) Hazard Ratio for OS

The efficacy evaluable population included all participants who received at least one dose of each study drug for their assigned treatment regimen.

Overall Survival (OS)

Difference in OS event-free rate at 3 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Imprime PGG + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Isatuximab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Selicrelumab + Bevacizumab vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Idasanutlin vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Regorafenib vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 6 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 12 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 18 months for the Atezolizumab + Regorafenib + AB928 vs. Regorafenib (Control) arms

Difference in OS event-free rate at 3 months for the Atezolizumab +LOAd703 vs. Regorafenib (Control) arms

3 Months

6 Months

12 Months

18 Months

The efficacy evaluable population included all participants who received at least one dose of each study drug for their assigned treatment regimen. The number analyzed at each landmark timepoint indicates the number of participants who were remaining at risk for an event. The event-free rate was not estimable (NE) for landmark timepoints at which 0 participants were remaining at risk for an an event.

Percentage of Participants Who Were Alive at Landmark Timepoints for Overall Survival (OS)

The duration of response analysis included all participants from the efficacy evaluable population who had a confirmed overall response; only 1 participant in each of the atezolizumab + regorafenib arm and the atezolizumab + regorafenib + AB928 arm had a confirmed response.

Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1

Disease Control Rate (DCR), as Determined by the Investigator Per RECIST v1.1

Adverse Event (AE)

Death

Withdrawn from Stage due to an AE

AE with a Fatal Outcome

Serious AE (SAE)

SAE Leading to Withdrawal from any Treatment

SAE Leading to Dose Modification/Interruption

Related SAE

AE Leading to Withdrawal from any Treatment

AE Leading to Dose Modification/Interruption

Related AE

Related AE Leading to Withdrawal from any Treatment

Related AE Leading to Dose Modification/Interruption

Grade 3-5 AE

Worst Grade AE: 5

Worst Grade AE: 4

Worst Grade AE: 3

The safety-evaluable population included all patients who received any amount of dose of any component of study treatment.

Percentage of Participants With at Least One Adverse Event (AE)

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Prostatic Neoplasms

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Hormones

Adenosine

Quemliclustat

Subjects with metastatic prostate cancer will receive quemliclustat and etrumadenant for 4 weeks prior to metastasis-directed SBRT (Stereotactic Body Radiation Therapy). Within one week of completing SBRT, subjects will also start zimberelimab.

Etrumadenant

240 mg IV once every two weeks starting within 1 week of completing metastasis-directed SBRT

Zimberelimab

Standard of care metastasis-directed hypofractionated radiotherapy treatment starting 4 weeks (+/- 1 week) of starting Etrumadenant and Quemliclustat

Stereotactic Body Radiation Therapy

Catherine S. Spina, MD, PhD

Research Nurse Navigator

This study will evaluate the safety and effectiveness of a combination of study drugs including zimberelimab, etrumadenant, and quemliclustat in combination with metastasis-directed irradiation in men with hormone sensitive oligometastatic prostate cancer.

The study aims to test the hypothesis that targeted inhibition of the adenosine signaling axis (quemliclustat (CD73 antagonist) + etrumadenant (A2AR/A2BR antagonist)) and immune checkpoint inhibition (zimberelimab, α-PD-1) in combination with metastasis-directed stereotactic body radiation therapy (SBRT) will improve local control, progression-free survival (PFS), and hormone therapy-free survival and mitigate immunosuppressive changes to the tumor microenvironment (TME), compared to SBRT alone.

The optimal therapeutic approach to men with oligometastatic (1-3 or 1-5 sites of metastatic disease) prostate cancer is ever more important as advanced imaging technologies are becoming standard of care, providing clinicians with the tools to accurately diagnose and localize oligometastatic prostate cancer. Hence, methods to improve the local curative potential of stereotactic body radiation therapy (SBRT) is a timely and important opportunity. In addition, previous data suggest that the adenosine A2A pathway may be a particularly attractive avenue for intervention in the context of radiation, thus influencing multiple suppressive populations within the tumor microenvironment (TME).

Immunotherapy based on the PD-1/PD-L1 signaling axis is a mainstay of therapy across multiple types of malignancies. This study aims to evaluate the effectiveness of a PD-1 inhibitor (zimberelimab) in combination with a selective dual antagonist of A2aR and A2bR (etrumadenant) and an anti-CD73 (quemliclustat). Immune checkpoint inhibitors and targeted inhibitors of the adenosine signaling axis modulate the TME and aspects of the systemic immune system to overcome tumor-induced immune suppression and improve responses to therapy.

This study aims to determine the effect of etrumadenant, quemliclustat and zimberelimab \[experimental\] when given with ablative radiation (SBRT)\[standard of care\] on the oligoprogressive disease (hormone sensitive oligometastatic prostate cancer), defined by being free from radiographic progression of irradiated target metastases and PSA (prostate surface antigen) response at 6 months. PSA response, local control, progression-free survival (PFS), treatment response, ADT-free survival, time-to-pain, and safety and tolerability will also be measured. By employing a Simon Two-Stage design, the trial will test whether or not etrumadenant + quemliclustat and zimberelimab combined with ablative radiation (SBRT) will improve PFS compared to SBRT alone (ORIOLE).

Simon Two-Stage design: In the first stage, trial will enroll 14 patients. If two or more patients show progression at 6 months, the study is terminated at the end of stage I. However, if 13 of the 14 remain free from progressive disease at 6 months, then the study would move onto the second stage. In this stage, n=9 additional patients will be enrolled, for a total of 23 total. If 21 of the 23 patients remain progression-free at 6 months, then the null hypothesis is rejected, and we will consider the addition of quemliclustat, etrumadenant, and zimberelimab to SBRT worthy of further study.

Adenosine Signaling Modulation and Immune Checkpoint Inhibition With Hormone Sensitive Oligometastatic Prostate Cancer

Phase II Single Arm Study Testing SBRT, Adenosine Signaling Modulation (AB680, AB928), and Immune Checkpoint Inhibition (AB122) for Men With Hormone Sensitive Oligometastatic Prostate Cancer

Biochemical recurrence is defined as a 0.2 ng/ml increase in PSA above the post-SBRT PSA nadir. Patient will be followed until biochemical recurrence, death, or end of study, whichever comes first. Patients who are alive and biochemical recurrence free will be censored at the last PSA measurement date.

To estimate the proportion of men treated with quemliclustat + etrumadenant + zimberelimab + SBRT who are free from biochemical failure at 6-months.

Report the percentage of patients with PD, CR, PR, and SD based on CT imaging among patients treated with oligometastasis-directed SBRT + quemliclustat + etrumadenant + zimberelimab at 6-months.

Report the percentage of patients with PD, CR, PR, and SD based on nuclear bone scan among patients treated with oligometastasis-directed SBRT + quemliclustat + etrumadenant + zimberelimab at 6-months.

Report the percentage of patients with PD, CR, PR, and SD based on PSMA-PET scan among patients treated with oligometastasis-directed SBRT + quemliclustat + etrumadenant + zimberelimab at 6-months.

Quantify pain using a numeric 10-point scale using the Brief Pain Inventory (BPI) every 12 weeks from time of enrollment.

Arcus Biosciences, Inc.

Catherine Spina

Assistant Professor of Radiation Oncology

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.

SRF617

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)	NCT03555149	Colorectal Canc...	Regorafenib Atezolizumab Imprime PGG Bevacizumab Isatuximab Selicrelumab Idasanutlin AB928 LOAd703	18 Years -	Hoffmann-La Roche
Adenosine Signaling Modulation and Immune Checkpoint Inhibition With Hormone Sensitive Oligometastatic Prostate Cancer	NCT05915442	Oligometastatic...	Quemliclustat Etrumadenant Zimberelimab Stereotactic Bo...	18 Years - 99 Years	Columbia University
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.
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)	NCT03555149	Colorectal Canc...	Regorafenib Atezolizumab Imprime PGG Bevacizumab Isatuximab Selicrelumab Idasanutlin AB928 LOAd703	18 Years -	Hoffmann-La Roche
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.
A Study Investigating the Safety, Absorption, and Elimination of Radioactively Labeled Etrumadenant, a New Compound in the Treatment of Cancer	NCT05411146	Healthy Partici...	[14C]-etrumaden...	18 Years - 55 Years	Arcus Biosciences, Inc.
A Study Investigating the Safety, Absorption, and Elimination of Radioactively Labeled Etrumadenant, a New Compound in the Treatment of Cancer	NCT05411146	Healthy Partici...	[14C]-etrumaden...	18 Years - 55 Years	Arcus Biosciences, Inc.

Spots Global Cancer Trial Database for ab928

Every month we try and update this database with for ab928 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 ab928

Every month we try and update this database with for ab928 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 ab928 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.