DCC-3116 + Anticancer Therapies for Advanced Cancers

Recruiting at 11 trial locations

Overseen By Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Deciphera Pharmaceuticals LLC

Must not be taking: CYP3A4 inhibitors, P-gp inducers

Disqualifiers: Heart disease, CNS metastases, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, DCC-3116, in combination with other cancer treatments to evaluate its effectiveness for people with advanced cancers. The primary focus is on individuals with a specific type of cancer called gastrointestinal stromal tumor (GIST), particularly those with certain mutations who have not responded well to previous treatments. Suitable candidates have GIST with a KIT or PDGFRA mutation, have not yet tried ripretinib (a cancer treatment), and have at least one measurable tumor. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including those that strongly affect liver enzymes (CYP3A4) or P-glycoprotein, at least 14 days before starting the study drug. You also need to avoid grapefruit and grapefruit juice for 14 days before the trial.

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

Research shows that the safety of DCC-3116, also known as inlexisertib, remains under investigation. In studies where it is combined with ripretinib, some safety information is available. Ripretinib alone has proven safer than sunitinib for patients with a specific type of cancer, suggesting that ripretinib is generally well-tolerated.

However, the safety of DCC-3116, especially in combination with ripretinib, is not yet fully understood. As this trial is in its early stages, researchers are still determining how well participants tolerate the combination and what side effects might occur. Participants in these trials help researchers learn more about safety and drug tolerance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DCC-3116, especially when used in combination with ripretinib, because it targets a unique pathway in cancer cells known as autophagy. Unlike traditional therapies for advanced gastrointestinal stromal tumors (GIST), which often focus on inhibiting growth signals or directly attacking cancer cells, DCC-3116 aims to block the cancer cells' survival mechanism by preventing them from recycling their own cellular components. This approach could potentially enhance the effectiveness of existing treatments like ripretinib, offering a new angle in the fight against GIST. By combining these therapies, there's hope for improved outcomes where conventional treatments may fall short.

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

Research has shown that combining two drugs, inlexisertib (DCC-3116) and ripretinib, may effectively treat advanced gastrointestinal stromal tumors (GIST). In this trial, certain participants will receive this combination to evaluate its efficacy. Early animal studies demonstrated that this combination made the tumors completely disappear. Ripretinib alone has already proven effective and safe as a second treatment option for advanced GIST, especially compared to another drug called sunitinib. Adding inlexisertib aims to enhance these effects, potentially increasing the treatment's effectiveness. Early results suggest this combination could be a strong choice for patients with this type of cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Clinical Team

Principal Investigator

Deciphera Pharmaceuticals, LLC

Are You a Good Fit for This Trial?

Adults with advanced colorectal cancer (CRC) having a specific mutation (BRAF V600E), or gastrointestinal stromal tumor (GIST) with certain mutations, who have tried some treatments but not others specified in the study criteria. Participants must be able to provide biopsy samples and have a life expectancy over 3 months.

Inclusion Criteria

My cancer can be measured by tests.

My colorectal cancer has a BRAF V600E mutation.

Must agree to provide an on treatment biopsy

Exclusion Criteria

Must not have received investigational therapies with unknown safety and PK profile within specified time periods prior to the first dose of study drug

I haven't taken strong or moderate drugs affecting CYP3A4 or P-gp, including St. John's wort, recently.

I haven't had grapefruit or its juice in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

DCC-3116 tablets in escalating dose cohorts in 28-day cycles will be administered in combination with ripretinib once daily (QD)

28-day cycles

Expansion

DCC-3116 tablets will be administered in combination with ripretinib in 28-day cycles to evaluate preliminary efficacy in participants with 2nd-line advanced gastrointestinal stromal tumor (GIST)

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• DCC-3116
• Encorafenib
• Ripretinib

Trial Overview The trial is testing DCC-3116 in combination with other anticancer drugs like Ripretinib, Cetuximab, and Encorafenib. It's an early-stage trial to see how well these combinations work together for treating CRC and GIST.

How Is the Trial Designed?

Group I: Expansion (Part 2, Module B) Experimental Treatment 2 Interventions

Inlexisertib tablets will be administered in combination with ripretinib in 28-day cycles to evaluate preliminary efficacy in participants with 2nd-line advanced gastrointestinal stromal tumor (GIST).

Group II: Expansion (Part 2, Module A) Experimental Treatment 1 Intervention

Expansion Module A Part 2 inlexisertib combination closed on January 8, 2024, with no participants enrolled.

Group III: Dose Escalation (Part 1, Module B) Experimental Treatment 2 Interventions

Inlexisertib tablets in escalating dose cohorts in 28-day cycles will be administered in combination with ripretinib once daily (QD).

Group IV: Dose Escalation (Part 1, Module A) Experimental Treatment 1 Intervention

Escalation Module A Part 1 inlexisertib combination closed on January 8, 2024, with no participants enrolled.

Who Is Running the Clinical Trial?

Deciphera Pharmaceuticals LLC

Lead Sponsor

Trials

17

Recruited

1,900+

Deciphera Pharmaceuticals, LLC

Lead Sponsor

Trials

19

Recruited

2,100+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Dicycloplatin (DCP) demonstrated a favorable safety profile in a Phase I study with 29 cancer patients, tolerating doses up to 550 mg/m², while showing potential efficacy with two partial responses in patients previously treated with other platinum-based chemotherapies.

DCP is stable in aqueous solution, which enhances its bioavailability and pharmacokinetics compared to carboplatin, making it a promising candidate for further clinical evaluation, with a recommended starting dose of 450 mg/m² for Phase II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of the novel platin complex dicycloplatin: clinical and pharmacokinetic results. Li, S., Huang, H., Liao, H., et al.[2013]

Combining dichloroacetate (DCA) with bevacizumab, an antiangiogenic drug, significantly inhibits tumor growth in glioblastoma models, suggesting a new strategy to overcome resistance to treatment.

The study found that DCA effectively reverses metabolic changes induced by bevacizumab, leading to improved outcomes in tumor growth control, highlighting the potential of targeting tumor metabolism alongside antiangiogenic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dichloroacetate reverses the hypoxic adaptation to bevacizumab and enhances its antitumor effects in mouse xenografts. Kumar, K., Wigfield, S., Gee, HE., et al.[2022]

In a phase 1 study involving 24 patients with advanced solid tumors, the recommended phase 2 dose (RP2D) of oral dichloroacetate (DCA) was determined to be 6.25 mg/kg twice daily, with manageable side effects primarily being grade 1-2 toxicities like fatigue and nausea.

While no significant tumor responses were observed, some patients experienced stable disease, and there was a trend indicating decreased (18) F-FDG uptake, suggesting potential metabolic changes with DCA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors. Chu, QS., Sangha, R., Spratlin, J., et al.[2018]

A comprehensive assessment identified 290 potential drug-drug interactions (DDIs) involving anticancer drugs, with 94 (32%) deemed clinically relevant, highlighting the importance of monitoring these interactions to ensure effective and safe cancer treatment.

The study emphasizes the need for integrating DDI guidelines into electronic prescribing systems to enhance patient safety and treatment efficacy, providing clinicians with a structured tool for managing DDIs in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence- and consensus-based guidelines for drug-drug interactions with anticancer drugs; A practical and universal tool for management. van Leeuwen, RWF., le Comte, M., Reyners, AKL., et al.[2022]

Antibody-drug conjugates (ADCs) are a promising treatment for breast cancer, effectively delivering cytotoxic drugs directly to tumors while minimizing systemic toxicity, making them generally well tolerated.

Despite their benefits, ADCs can cause predictable side effects such as neutropenia and nausea, which require careful monitoring and management to prevent treatment interruptions or dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of antibody-drug conjugates in breast cancer: practical considerations. D'Arienzo, A., Verrazzo, A., Pagliuca, M., et al.[2023]

The DCC gene was successfully transfected into the ovarian cancer cell line SKOV-3, leading to a significant reduction in cell proliferation and a lower half maximal inhibitory concentration (IC50) compared to control cells.

Expression of the DCC gene resulted in G1 phase cell cycle arrest and induced apoptosis in SKOV-3 cells, while in vivo studies showed that mice with SKOV-3/DCC cells had smaller tumor volumes and no tumorigenicity, suggesting a strong tumor-suppressive effect of the DCC gene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of deleted in colorectal carcinoma gene on proliferation of ovarian cancer cell line SKOV-3 in vivo and in vitro. Cai, Y., Hu, CJ., Wang, J., et al.[2019]

A systematic review of 128 randomized clinical trials involving 47,432 patients showed that anticancer drugs provided a statistically significant benefit in progression-free survival (PFS) and overall survival (OS) compared to best supportive care, with hazard ratios of 0.58 and 0.82, respectively.

Despite these benefits, the absolute gains in survival were modest, with PFS extending by only 2.1 months and OS by 0.5 months, and there was a weak correlation between severe toxicity and treatment efficacy, indicating that higher toxicity did not necessarily lead to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks and benefits of anticancer drugs in advanced cancer patients: A systematic review and meta-analysis. Moreau Bachelard, C., Coquan, E., du Rusquec, P., et al.[2022]

In a study analyzing 265 serious adverse drug reactions (ADRs) from oral protein kinase inhibitors (PKIs) in France, 63.8% of the ADRs were deemed 'unpreventable', indicating a high rate of unavoidable reactions in cancer treatment.

Only 1.5% of serious ADRs were identified as preventable or potentially preventable, suggesting that while some adverse reactions could be avoided with better prescribing practices, the overall rate of preventability is low, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventable and potentially preventable serious adverse reactions induced by oral protein kinase inhibitors through a database of adverse drug reaction reports. Egron, A., Olivier-Abbal, P., Gouraud, A., et al.[2021]

Antibody-drug conjugates (ADCs), particularly trastuzumab drug conjugates (T-DCs) like T-DM1 and T-Dxd, are emerging as effective treatments for HER2-positive and HER2-low solid tumors, showing promising efficacy in clinical trials.

While T-DCs demonstrate innovative pharmacokinetic and pharmacodynamic properties, they also present unique toxicity profiles, highlighting the need for careful monitoring and potential combination strategies with other therapies to enhance their effectiveness and manage resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving therapeutic landscape of trastuzumab-drug conjugates: Future perspectives beyond HER2-positive breast cancer. von Arx, C., De Placido, P., Caltavituro, A., et al.[2023]

Dichloroacetate (DCA) shows potential as an anticancer agent, particularly due to its ability to selectively target cancer cell metabolism, although its clinical use is still limited by side effects like neurotoxicity and concerns about carcinogenicity.

Recent studies suggest that DCA can be effectively combined with conventional cancer treatments and new drug delivery systems, enhancing its bioavailability and efficacy, especially against cancer stem cells, which could lead to improved cancer eradication strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications. Tataranni, T., Piccoli, C.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05957367

NCT05957367 | A Study of Inlexisertib (DCC-3116) in ... A Study of Inlexisertib (DCC-3116) in Combination With Anticancer Therapies in Participants With Advanced Malignancies · Study Overview · Contacts and Locations.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS11587

DCC-3116 in combination with ripretinib for patients ... In the INTRIGUE trial, ripretinib demonstrated comparable efficacy and more favorable safety compared with sunitinib in second-line advanced ...

3. onclive.com onclive.com/view/dr-kelly-on-the-evaluation-of-the-combination-of-ripretinib-and-dcc-3116-in-gist

Dr Kelly on the Evaluation of the Combination of Ripretinib ... In preclinical models of GIST, the combination of ripretinib and DCC-3116 was shown to be highly effective, leading to complete tumor regression ...

4. deciphera.com deciphera.com/news/deciphera-pharmaceuticals-announces-oral-presentation-results-motion-pivotal-phase-3-study

Deciphera Pharmaceuticals Announces Oral Presentation ... MOTION Phase 3 Data Demonstrate Robust Efficacy, Clinically Meaningful Improvements in Quality-of-Life Measures, and Well-Tolerated Safety ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-of-dcc-3116-and-ripretinib-for-patients-with-advanced-gastrointestinal-stromal-tumor-gist/

Study of DCC-3116 and ripretinib combination therapy in ... This clinical trial investigates the effects of DCC-3116 and Ripretinib on patients with advanced gastrointestinal stromal tumors (GIST), ...

6. gisttrials.org gisttrials.org/iLRG/details.php?Trial=400

trial detail - GIST clinical trials Trial Detail: A Study of DCC-3116 in Combination with Anticancer Therapies in Participants with Advanced Malignancies.

7. delta.larvol.com delta.larvol.com/Products/?ProductId=e913a8aa-bca1-4a4c-acbc-94b41ccab8b9

inlexisertib (DCC-3116) / Ono Pharma Delicious. April 25, 2024. DCC-3116 in combination with ripretinib for patients with advanced gastrointestinal stromal tumor: A phase 1/2 study. (ASCO 2024) ...