What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, particularly those involving PD-L1 inhibitors like Atezolizumab and Avelumab, can cause immune-related side effects such as fatigue, rash, diarrhea, and liver enzyme abnormalities. Chemotherapy regimens like FOLFOX often result in nausea, vomiting, neuropathy, myelosuppression, and mucositis. Combining these treatments may increase the risk of overlapping toxicities, especially gastrointestinal and hematologic side effects.

What prior FDA approvals exist?

The FDA has approved several immunotherapy treatments for colorectal cancer, particularly for cases with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H). Pembrolizumab (Keytruda) and Nivolumab (Opdivo) are approved as single-agent therapies, and the combination of Nivolumab with Ipilimumab (Yervoy) is also approved for metastatic CRC that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan. These treatments target the PD-1/PD-L1 pathway, similar to the investigational combinations involving Atezolizumab and Avelumab in the XL092 trial.

What other types of research exist?

Promising alternatives to XL092 in combination with atezolizumab and avelumab for colorectal cancer patients include: 1) Bevacizumab in combination with fluoropyrimidine-based chemotherapy (e.g., XELOX or FOLFOX), which has shown efficacy in first-line treatment of metastatic colorectal cancer. 2) Simtuzumab in combination with FOLFIRI, although it did not improve clinical outcomes in KRAS mutant colorectal carcinoma, it remains a potential option in combination with other agents. 3) Pembrolizumab, especially for patients with high PD-L1 expression, either as monotherapy or in combination with chemotherapy.

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XL092 + Immunotherapy for Cancer (STELLAR-001 Trial)

Phase 1

Waitlist Available

Research Sponsored by Exelixis

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Female subjects of childbearing potential must not be pregnant at screening

Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum, KRAS/NRAS wild-type (confirmed via local testing report) and determined NOT to have microsatellite instability high (MSI-high) or mismatch repair deficient (dMMR) by local testing, who received specific standard of care chemotherapy regimens as prior therapy for metastatic CRC

Must not have

Prior treatment with XL092 (all cohorts), prior treatment with PD-L1/PD-1 targeting immune checkpoint inhibitor (Cohorts E, F, G, and H only), or prior treatment with regorafenib and/or TAS-102 (Cohort H only)

Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 36 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called XL092 by itself and with two other drugs, atezolizumab and avelumab. It targets patients with advanced solid tumors who may not respond to current treatments. XL092 aims to stop cancer cells from growing, while atezolizumab and avelumab help the immune system fight the cancer. Atezolizumab is approved for various cancers, including breast and urothelial carcinoma, and has shown efficacy in combination with chemotherapy.

Who is the study for?

This trial is for adults with advanced solid tumors that are inoperable or metastatic, and who have tried other treatments without success. They must be mostly recovered from previous treatment side effects, not pregnant, able to use contraception, and have good organ function. People with certain cancers like colorectal cancer must meet specific genetic criteria.

What is being tested?

The study tests XL092 alone or combined with Atezolizumab or Avelumab in patients with various solid tumors. It's an early-phase trial to check safety, how the body processes the drugs (pharmacokinetics), their effect on tumor markers, and initial effectiveness against the cancer.

What are the potential side effects?

Possible side effects include typical reactions to immune therapies such as fatigue, skin issues, inflammation of organs (like colitis), potential infusion-related reactions and possibly changes in liver enzymes which could indicate liver issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am not pregnant and can become pregnant.

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My colon or rectum cancer is advanced, cannot be surgically removed, and lacks certain genetic mutations.

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I have advanced kidney cancer that's not clear cell type and it has worsened after at least one treatment.

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My cancer cannot be surgically removed, has spread, and no treatments work or can be tolerated.

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I can provide a sample of my tumor for the study.

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My kidney cancer has worsened after at least one treatment.

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My breast cancer is hormone receptor positive, HER2 negative, and has worsened despite treatment.

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I am using reliable birth control methods if I'm sexually active.

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I am fully active or can carry out light work.

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My cancer is advanced, cannot be removed by surgery, and may have spread or come back.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have previously been treated with XL092, PD-L1/PD-1 inhibitors, regorafenib, or TAS-102 depending on my trial cohort.

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I haven't had radiation for bone metastasis in the last 2 weeks or any other radiation in the last 4 weeks.

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I do not have any recent or ongoing serious illnesses.

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I am taking other medications.

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My heart's electrical activity, measured by QTcF, is within normal range.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 36 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 36 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 36 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cohort-Expansion Stage (Cohort H only): Overall Survival (OS)

Cohort-Expansion Stage (except Cohort H): Progression-Free Survival (PFS)

Cohort-Expansion Stage: Objective Response Rate (ORR)

+1 more

Secondary study objectives

Dose-Escalation Stage: Apparent Clearance (CL/F)

Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24)

Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: XL092 Single-Agent Expansion CohortsExperimental Treatment1 Intervention

The MTD or recommended dose from the dose-escalation stage may be further explored in clear cell renal cell carcinoma (ccRCC), non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), and metastatic castration-resistant prostate cancer (mCRPC).

Group II: XL092 Single-Agent Dose-Escalation CohortsExperimental Treatment1 Intervention

Subjects will accrue in cohorts of 3-6 subjects in a standard "3 plus 3" design.

Group III: XL092 + Avelumab Dose-Escalation CohortsExperimental Treatment2 Interventions

Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.

Group IV: XL092 + Atezolizumab Expansion CohortsExperimental Treatment2 Interventions

The MTD or recommended dose from the dose-escalation stage may be further explored in non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), metastatic castration-resistant prostate cancer (mCRPC), and colorectal cancer (CRC).

Group V: XL092 + Atezolizumab Dose-Escalation CohortsExperimental Treatment2 Interventions

Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atezolizumab

2016

Completed Phase 3

~5860

Avelumab

2017

Completed Phase 2

~2440

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Colorectal cancer treatments often include immune checkpoint inhibitors like Atezolizumab and Avelumab, which target the PD-L1 protein. These drugs work by blocking the interaction between PD-L1 on tumor cells and PD-1 on T cells, thereby preventing the 'off' signal that allows cancer cells to evade the immune system. This reactivates T cells to recognize and attack cancer cells. Other common treatments include chemotherapy agents like fluoropyrimidines and oxaliplatin, which kill rapidly dividing cells, and targeted therapies like bevacizumab, which inhibits angiogenesis. Understanding these mechanisms is crucial for colorectal cancer patients as it helps in selecting the most effective treatment strategy and managing potential side effects.

Systemic Treatments for Advanced Small Bowel Adenocarcinoma: A Systematic Review.Maintenance avelumab versus continuation of first-line chemotherapy in gastric cancer: JAVELIN Gastric 100 study design.Small bowel adenocarcinomas--existing evidence and evolving paradigms.