DCC-3116 for Solid Tumors
Recruiting in Palo Alto (17 mi)
+10 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Deciphera Pharmaceuticals LLC
Must not be taking: CYP3A4 inhibitors, P-gp inducers
Disqualifiers: CNS metastases, Heart disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This trial tests a new drug, DCC-3116, alone and with other drugs, in patients with advanced cancers that have specific genetic mutations. The drug works by blocking a pathway that helps cancer cells grow.
Will I have to stop taking my current medications?
You may need to stop taking certain medications before joining the trial. Specifically, you must not have taken strong or moderate inhibitors or inducers of CYP3A4 or P-glycoprotein, including some herbal medications, within 14 days or 5 times the medication's half-life. Additionally, you must stop taking grapefruit products 14 days before starting the study.
What data supports the effectiveness of the drug DCC-3116 for solid tumors?
Research shows that binimetinib, a component of the treatment, is effective in treating melanoma with specific genetic mutations. Additionally, combining BRAF and MEK inhibitors, like binimetinib and trametinib, has shown positive results in treating certain lung cancers, suggesting potential effectiveness in other solid tumors.12345
What safety information is available for DCC-3116 and related treatments?
What makes the drug combination of DCC-3116, Binimetinib, Sotorasib, and Trametinib unique for treating solid tumors?
This drug combination is unique because it targets multiple pathways involved in tumor growth and survival, potentially offering a more comprehensive approach to treating solid tumors compared to single-agent therapies. Each component, like Sotorasib, which targets a specific mutation in cancer cells, adds a layer of specificity and potential effectiveness.910111213
Research Team
CT
Clinical Team
Principal Investigator
Deciphera Pharmaceuticals, LLC
Eligibility Criteria
Adults with advanced solid tumors having specific mutations (RAS/MAPK pathway) who've had certain prior treatments can join. They need good organ function, an ECOG score of 0-2, and must not be pregnant or breastfeeding. Contraception is required for both men and women.Inclusion Criteria
My cancer has a KRAS G12C mutation.
I can provide a new or old sample of my tumor for the study.
I agree to follow the required contraception methods.
See 27 more
Exclusion Criteria
Known human immunodeficiency virus unless the following requirements are met:
I haven't taken any experimental drugs with unknown safety for at least 28 days, or 14 days with approval.
I stopped taking trametinib or binimetinib due to side effects.
See 24 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
DCC-3116 is administered in escalating doses as monotherapy and in combination with other drugs to determine the maximum tolerated dose
Approximately 18 months
Expansion
DCC-3116 is administered in combination with sotorasib in 28-day cycles to evaluate safety and preliminary efficacy
Approximately 24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Binimetinib (MAPK Pathway Inhibitor)
- DCC-3116 (MAPK Pathway Inhibitor)
- Sotorasib (MAPK Pathway Inhibitor)
- Trametinib (MAPK Pathway Inhibitor)
Trial OverviewThe trial tests DCC-3116 alone or with trametinib, binimetinib, or sotorasib in two phases: dose escalation to find safe amounts and expansion to see effects on different cancers like colorectal cancer and melanoma.
Participant Groups
6Treatment groups
Experimental Treatment
Group I: Expansion Cohorts 1, 2, 3 and 4 (Part 2)Experimental Treatment1 Intervention
Expansion Cohorts 1, 2, 3 and 4 DCC-3116 combinations will not open for enrollment.
Group II: Expansion Cohort 5 (Part 2)Experimental Treatment2 Interventions
DCC-3116 tablets orally given in combination with sotorasib in 28-day cycles to evaluate safety and preliminary efficacy of participants with NSCLC (with a documented mutation in KRAS G12C).
Group III: Dose Escalation (Part 1, Cohort D Combination)Experimental Treatment2 Interventions
Upon determination of the RP2D/MTD single agent, DCC-3116 will be dosed in combination with sotorasib.
Group IV: Dose Escalation (Part 1, Cohort C Combination)Experimental Treatment2 Interventions
Upon determination of the RP2D/MTD single agent, DCC-3116 will be dosed in combination with binimetinib.
Escalation Cohort C combination closed on January 8, 2024.
Group V: Dose Escalation (Part 1, Cohort B Combination)Experimental Treatment2 Interventions
Upon determination of the RP2D/MTD single agent, DCC-3116 will be dosed in combination with trametinib.
Escalation Cohort B combination closed on January 8, 2024.
Group VI: Dose Escalation (Part 1, Cohort A Monotherapy)Experimental Treatment1 Intervention
DCC-3116 tablets in escalating dose cohorts given orally twice daily (BID) in 28-day cycles as monotherapy (single agent). If no DLT in 3 participants or 1 DLT/6 participants is observed, dose escalation may continue to the next planned dose cohort.
Binimetinib is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Mektovi for:
- Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
🇪🇺 Approved in European Union as Mektovi for:
- Unresectable or metastatic melanoma with a BRAF V600 mutation
🇨🇦 Approved in Canada as Mektovi for:
- Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
🇯🇵 Approved in Japan as Mektovi for:
- Unresectable or metastatic melanoma with a BRAF V600 mutation
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Rutgers Cancer InstituteNew Brunswick, NJ
NEXT OncologySan Antonio, TX
Washington University Siteman Cancer CenterSaint Louis, MO
Siteman Cancer CenterSaint Louis, MO
More Trial Locations
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Who Is Running the Clinical Trial?
Deciphera Pharmaceuticals LLC
Lead Sponsor
Trials
17
Patients Recruited
1,900+
Deciphera Pharmaceuticals, LLC
Lead Sponsor
Trials
19
Patients Recruited
2,100+
Findings from Research
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
The discovery and development of binimetinib for the treatment of melanoma.Tran, B., Cohen, MS.[2021]
In a phase II study involving 183 metastatic melanoma patients, binimetinib effectively inhibited the MAPK pathway, as evidenced by decreased levels of pERK and DUSP6 in tumor samples after treatment.
Despite the observed pathway inhibition, there was no direct correlation between reduced pERK or DUSP6 levels and clinical efficacy, suggesting that additional genetic factors, such as alterations in CDKN2A/B and PTEN, may influence treatment outcomes.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Biomarker results from a phase II study of MEK1/2 inhibitor binimetinib (MEK162) in patients with advanced NRAS- or BRAF-mutated melanoma.van Herpen, CML., Agarwala, SS., Hauschild, A., et al.[2020]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
BRAF Inhibitors in Non-Small Cell Lung Cancer.Sforza, V., Palumbo, G., Cascetta, P., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective.Halloush, S., Alkhatib, NS., Almutairi, AR., et al.[2023]
In a study involving 21 Japanese patients with advanced solid tumors, binimetinib was found to have an acceptable safety profile, with the maximum tolerated dose established at 45 mg taken twice daily, despite some patients experiencing reversible retinal adverse events.
While no complete or partial responses were observed, 67% of patients achieved stable disease for over 180 days, indicating that binimetinib can effectively stabilize tumor growth in this patient population.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors.Watanabe, K., Otsu, S., Hirashima, Y., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer.Riely, GJ., Smit, EF., Ahn, MJ., et al.[2023]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma.van Dijk, EH., van Herpen, CM., Marinkovic, M., et al.[2023]
In a study involving 28 patients with advanced biliary tract cancer, binimetinib was found to be well tolerated, with common mild side effects like rash (82%) and nausea (54%), and only two patients experienced severe adverse events.
Binimetinib demonstrated promising clinical activity, with 43% of patients achieving stable disease and two patients showing objective responses, including one complete response, suggesting its potential effectiveness in treating this type of cancer.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer.Finn, RS., Ahn, DH., Javle, MM., et al.[2019]
Sunitinib is an effective small-molecule inhibitor that targets receptor tyrosine kinases involved in tumor blood vessel formation, particularly the VEGF receptor, showing significant antiangiogenic effects in laboratory and animal studies.
In human trials, a daily dose of 50 mg has been found to be tolerable and effective, especially for advanced renal cell carcinoma and gastrointestinal stromal tumors that are resistant to imatinib, leading to its regulatory approval for these conditions.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Sunitinib.Rini, BI.[2019]
Temsirolimus, an mTOR-inhibitor, showed prolonged activity in a patient with desmoplastic small round cell tumor (DSRCT), suggesting potential therapeutic benefits for this aggressive cancer.
In vitro studies indicated that rapamycin can induce cell death in JN-DSRCT-1 cells, which may help in understanding the mechanism of action for mTOR inhibitors in treating DSRCT.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Temsirolimus for metastatic desmoplastic small round cell tumor.Thijs, AM., van der Graaf, WT., van Herpen, CM.[2022]
The combination of sunitinib and tremelimumab in patients with metastatic renal cell carcinoma showed significant safety concerns, particularly with rapid-onset acute renal failure being the most common dose-limiting toxicity observed.
Despite the safety issues, the treatment demonstrated some efficacy, with 43% of evaluable patients achieving partial responses, indicating potential antitumor activity that warrants further investigation.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Phase 1 dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma.Rini, BI., Stein, M., Shannon, P., et al.[2020]
In a Phase II trial involving 13 patients with desmoplastic small round cell tumor (DSRCT) who were unresponsive to conventional treatments, imatinib was administered at a dose of 400 mg daily.
The results showed that imatinib had no significant efficacy, with only one patient achieving stable disease and seven experiencing progressive disease after three months.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Imatinib mesylate in desmoplastic small round cell tumors.De Sanctis, R., Bertuzzi, A., Bisogno, G., et al.[2018]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12).Zhou, C., Wu, L., Fan, Y., et al.[2022]
References
The discovery and development of binimetinib for the treatment of melanoma. [2021]
Biomarker results from a phase II study of MEK1/2 inhibitor binimetinib (MEK162) in patients with advanced NRAS- or BRAF-mutated melanoma. [2020]
BRAF Inhibitors in Non-Small Cell Lung Cancer. [2022]
Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective. [2023]
A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors. [2022]
Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. [2023]
Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma. [2023]
Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer. [2019]
Sunitinib. [2019]
Temsirolimus for metastatic desmoplastic small round cell tumor. [2022]
Phase 1 dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma. [2020]
Imatinib mesylate in desmoplastic small round cell tumors. [2018]
Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12). [2022]