XL495 for Cancer

No longer recruiting at 10 trial locations

Overseen By Exelixis Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Exelixis

Disqualifiers: Brain metastases, Severe illness, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment called XL495, an experimental therapy, to determine its safety and effectiveness both alone and with other cancer-fighting drugs. It targets individuals with advanced cancers where other treatments have failed or are too harsh to continue. Participants should have tried up to three other treatments and have advanced cancer that has spread, such as bladder cancer. This trial offers a potential new option when other treatments are no longer viable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that prior anticancer treatment like radiation therapy should not have been received within 2 weeks before the first dose of the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research suggests that XL495 might fight tumors both alone and in combination with other drugs that damage cancer cell DNA. However, no published studies have yet confirmed its safety in humans. As this trial is in the early stages (Phase 1), information on how well people tolerate XL495 remains limited. Early-stage trials primarily focus on assessing safety and determining the correct dosage.

When combined with Antibody Drug Conjugates (ADCs), these ADCs aim to target cancer cells directly, potentially reducing side effects on healthy cells. However, this combination is still under investigation, and complete safety information is not yet available. Participants are closely monitored to assess their response to these treatments and to identify any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about XL495 because it offers a novel approach for treating advanced metastatic tumors, including urothelial cancer. Unlike standard treatments like chemotherapy and targeted therapy, XL495 is being tested both alone and in combination with Antibody Drug Conjugate (ADC) cytotoxic agents. This combination aims to enhance the precision of cancer cell targeting while minimizing damage to healthy cells. The unique action of XL495, potentially in combination with ADCs, could lead to more effective treatment outcomes and reduced side effects compared to traditional options.

What evidence suggests that this trial's treatments could be effective for cancer?

Studies have shown that XL495 has promising activity against tumors. Early research indicated that cancer cells with a specific gene called CCNE1 responded better to XL495, suggesting it might be more effective for certain cancer types. In this trial, some participants will receive XL495 alone, while others will receive it combined with ADCs (antibody-drug conjugates), which could enhance its effectiveness. ADCs have successfully treated various cancers by delivering drugs directly to cancer cells. These findings suggest potential benefits, but further studies in humans are needed to confirm XL495's effectiveness. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors who've had 1-3 prior treatments and no life-prolonging options left. They must have a measurable tumor, be fit enough for treatment (ECOG 0-2), and can't join if they've had certain transplants, active hepatitis, severe recent illness, brain metastases, or HIV.

Inclusion Criteria

Participants must have at least one measurable lesion as defined by RECIST, version 1.1.

I have tried at least one standard treatment for my condition, or none are suitable for me.

I have tried or cannot use certain targeted cancer drugs due to side effects, ineligibility, or personal choice.

Exclusion Criteria

I have HIV but meet the specific health criteria.

I have a condition that prevents my body from absorbing nutrients properly.

I have brain metastases or cranial epidural disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants with advanced metastatic tumors receive increasing doses of XL495

Variable duration until maximum tolerated dose is determined

Dose Finding

Participants receive XL495 and ADC cytotoxic agents together at increasing doses

Variable duration until recommended dosage is determined

Expansion

Participants with urothelial cancer receive XL495 and ADC cytotoxic agents at the recommended dosage(s)

Until disease progression or death, up to approximately 19 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ADC cytotoxic agents
• XL495

Trial Overview The study tests the safety and cancer-fighting ability of XL495 alone or with other drugs in patients whose tumors have spread. It's looking at how well people tolerate it, its pharmacokinetics (how the body processes it), and initial effectiveness against tumors.

How Is the Trial Designed?

Group I: Expansion XL495 + ADC cytotoxic agents Experimental Treatment 2 Interventions

Group(s) of participants with urothelial cancer who will receive XL495 and ADC cytotoxic agents at the recommended dosage(s) of expansion (RDE \[s\]) determined during the dose-escalation and dose-finding stages.

Group II: Dose Finding XL495 + ADC cytotoxic agents Experimental Treatment 2 Interventions

Group(s) of participants with advanced metastatic tumors who will receive XL495 and Antibody drug conjugate (ADC) cytotoxic agents together at increasing doses.

Group III: Dose Escalation XL495 Experimental Treatment 1 Intervention

Group(s) of participants with advanced metastatic tumors who will receive increasing doses of XL495.

Who Is Running the Clinical Trial?

Exelixis

Lead Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

In a study of 37 advanced ovarian cancer patients treated with oxaliplatin and paclitaxel, the combination showed a promising objective response rate of 48%, with 1 complete and 14 partial responses, indicating its potential efficacy, especially in platinum-resistant cases.

Despite some toxicity, including neutropenia and peripheral neuropathy, the treatment demonstrated a median progression-free survival of 9 months and an overall survival of 25.2 months, suggesting it could be a valuable salvage therapy for patients with limited options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin and paclitaxel combination in patients with platinum-pretreated ovarian carcinoma: an investigator-originated compassionate-use experience. Faivre, S., Kalla, S., Cvitkovic, E., et al.[2020]

In a phase III study involving 240 patients with locally advanced unresectable non-small-cell lung cancer (NSCLC), adding cisplatin to radiation therapy did not significantly improve overall survival or progression-free survival compared to radiation therapy alone.

The overall response rate was slightly higher in the combination group (50%) compared to radiation alone (38%), but this difference was not statistically significant, indicating that cisplatin may not provide additional benefits in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small-cell lung cancer: a Hoosier Oncology Group protocol. Blanke, C., Ansari, R., Mantravadi, R., et al.[2017]

In a study of 36 patients with recurrent epithelial ovarian cancer, the combination of docetaxel (DTX) and oxaliplatin (OXA) resulted in an overall response rate of 55.6%, with 8.3% achieving complete responses and 47.2% showing partial responses.

The treatment was found to have a tolerable safety profile, with the main side effects being hematological toxicities and peripheral neuropathy, indicating that while effective, monitoring for these adverse effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic effect of docetaxel combined with oxaliplatin for treatment of recurrent epithelial ovarian cancer]. Wang, J., Han, N., Wang, HL., et al.[2018]

The study identified a novel XLF inhibitor, G3, which significantly enhances the effectiveness of 5-fluorouracil (5-Fu) and oxaliplatin (OXA) in chemoresistant colorectal cancer (CRC) cells, with an IC50 of 0.47 µM.

G3 works by degrading XLF protein, which disrupts DNA repair mechanisms, specifically nonhomologous end joining (NHEJ) and homologous recombination (HR), thereby increasing the sensitivity of CRC cells to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification Of Natural Compound Derivative For Inhibition Of XLF And Overcoming Chemoresistance In Colorectal Cancer Cells. Liu, Z., Yu, M., Fei, B., et al.[2022]

Paclitaxel has shown promising efficacy in treating stage IV breast cancer, with overall response rates ranging from 44% to 62% in phase II trials, indicating it can be an effective option for patients with limited prior therapy.

The treatment is generally well tolerated, with febrile neutropenia being the most common side effect, and it has demonstrated safety and efficacy even in patients with extensive prior therapy, achieving response rates of 36% in those with two prior treatments and 21% in those with three or more.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent use of Taxol (paclitaxel) in breast cancer. Seidman, AD.[2016]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/1733/756159/Abstract-1733-XL495-is-a-potent-selective-and

Abstract 1733: XL495 is a potent, selective, and orally ... Cancer cell lines with CCNE1 amplification were more sensitive to XL495 than other models. XL495 demonstrated dose-dependent antitumor activity ...

2. withpower.com withpower.com/trial/xl495-for-cancer-cc935

XL495 for Cancer · Info for Participants The research does not provide direct evidence for the effectiveness of XL495, but it mentions the use of similar treatments like paclitaxel, which has shown ...

3. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-present-positive-preclinical-data-across-its-pipeline

Exelixis to Present Positive Preclinical Data Across Its Pipeline ... Data from the analysis show XL495 has demonstrated the potential for anti-tumor activity alone and in combination with DNA-damaging agents. A ...

4. bcan.org bcan.org/clinicaltrials/xl495-in-participants-with-locally-advanced-or-metastatic-solid-tumors/

XL495 in Participants With Locally Advanced or Metastatic ... The goal of this study is to obtain safety, tolerability, PK, and preliminary clinical antitumor activity for XL495 as a single agent and in combination with ...

5. trial.medpath.com trial.medpath.com/clinical-trial/e6a275380b5d97d2/nct06630247-dose-escalation-xl495-solid-tumors

A Dose-escalation, Dose-finding, and Expansion Study of ... The goal of this study is to obtain safety, tolerability, PK, and preliminary clinical antitumor activity for XL495 as a single agent and in combination ...

6. ctv.veeva.com ctv.veeva.com/study/a-dose-escalation-dose-finding-and-expansion-study-of-xl495-in-participants-with-locally-advanced

A Dose-escalation, Dose-finding, and Expansion Study of ... The goal of this study is to obtain safety, tolerability, PK, and preliminary clinical antitumor activity for XL495 as a single agent and in ...