INCB0123667 for Solid Tumors

Recruiting at57 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Incyte Corporation

Must not be taking: CDK2 inhibitors

Disqualifiers: Cardiac disease, Untreated CNS metastases, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called INCB123667 to see if it can help treat advanced or spreading cancers. It aims to find out how safe and effective the drug is, and how the body processes it. The study focuses on patients whose cancers are advanced or have spread.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have any change in endocrine therapy or take certain treatments within 28 days before starting the study drug.

How does the drug INCB123667 differ from other treatments for solid tumors?

INCB123667 is unique because it targets the mTOR pathway, which is often dysregulated in cancer, and may offer a novel approach to treating solid tumors by potentially overcoming drug resistance seen with first-generation mTOR inhibitors. ^{1 2 3 4 5}

Research Team

Liz Croft, MD

Principal Investigator

Incyte Corporation

Eligibility Criteria

This trial is for adults with advanced solid tumors, including specific types such as gynecologic, gastrointestinal, and breast cancers. Participants must have a performance status indicating they are relatively active and capable of self-care. They should have measurable lesions not suitable for curative treatments and be willing to provide tumor specimens. Pregnant or breastfeeding individuals cannot join, nor can those with certain heart conditions, uncontrolled diseases, recent other cancer treatments or surgeries.

Inclusion Criteria

My condition worsened after standard treatment, or I can't tolerate/have no other treatment options.

I am between 18 and 99 years old, living in France.

Life expectancy greater than 12 weeks

Exclusion Criteria

I am not taking any medications that are not allowed in the study.

I have no other cancer needing treatment or that has been active in the last 2 years, except for certain skin cancers or other minor cancers treated over a year ago.

I have been diagnosed with HIV.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

INCB123667 is administered in escalating doses to determine safety and tolerability

28 days per cycle

Cycle 1 Days 1, 2, 8 and 9; Cycle 2 Day 1; Cycles 3 through 9 Day 1

Dose Expansion

INCB123667 is administered at the recommended dose for expansion to evaluate efficacy

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• INCB123667 (Other)

Trial Overview The study tests INCB123667's safety and effectiveness in treating advanced solid tumors. It has two parts: dose escalation to find the maximum tolerated dose (MTD) and recommended dose for expansion (RDE), followed by a cohort expansion phase at the RDE to assess antitumor activity across six different tumor-specific groups.

Participant Groups

Group I: Phase 2b Dose Expansion Treatment Group N (TGN) Experimental Treatment 2 Interventions

INCB123667 administered in combination with weekly paclitaxel at the recommended doses in participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) as defined by the protocol.

Group II: Phase 2b Dose Expansion Treatment Group M (TGM) Experimental Treatment 2 Interventions

INCB123667 administered in combination with olaparib at the recommended doses in participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) as defined by the protocol.

Group III: Phase 2b Dose Expansion Treatment Group L (TGL) Experimental Treatment 2 Interventions

INCB123667 administered in combination with bevacizumab at the recommended doses in participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) as defined by the protocol.

Group IV: Phase 2b Dose Expansion Treatment Group K (TGK) Experimental Treatment 3 Interventions

INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol.

Group V: Phase 2b Dose Expansion Treatment Group J (TGJ) Experimental Treatment 2 Interventions

INCB123667 administered in combination with ribociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Group VI: Phase 2b Dose Expansion Treatment Group I (TGI) Experimental Treatment 3 Interventions

INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol

Group VII: Phase 2b Dose Expansion Treatment Group H (TGH) Experimental Treatment 2 Interventions

INCB123667 administered in combination with palbociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Group VIII: Phase 2a Dose Escalation Treatment Group G (TGG) Experimental Treatment 2 Interventions

INCB123667 administered in combination with paclitaxel at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Group IX: Phase 2a Dose Escalation Treatment Group F (TGF) Experimental Treatment 2 Interventions

INCB123667 administered in combination with olaparib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Group X: Phase 2a Dose Escalation Treatment Group E (TGE) Experimental Treatment 2 Interventions

INCB123667 administered in combination with bevacizumab at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Group XI: Phase 2a Dose Escalation Treatment Group D (TGD) Experimental Treatment 3 Interventions

INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol.

Group XII: Phase 2a Dose Escalation Treatment Group C (TGC) Experimental Treatment 2 Interventions

INCB123667 administered in combination with ribociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Group XIII: Phase 2a Dose Escalation Treatment Group B (TGB) Experimental Treatment 3 Interventions

INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol.

Group XIV: Phase 2a Dose Escalation Treatment Group A (TGA) Experimental Treatment 2 Interventions

INCB123667 administered in combination with palbociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Group XV: Phase 1b: Dose Expansion Cohort Disease Group 6 Experimental Treatment 1 Intervention

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors will enroll in this group.

Group XVI: Phase 1b: Dose Expansion Cohort Disease Group 5 Experimental Treatment 1 Intervention

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with HR+/HER2- breast cancer who have had disease progression on or been intolerant of a CDK4/6 inhibitor will enroll in this group.

Group XVII: Phase 1b: Dose Expansion Cohort Disease Group 4 Experimental Treatment 1 Intervention

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with Triple Negative Breast Cancer(TNBC) will enroll in this group.

Group XVIII: Phase 1b: Dose Expansion Cohort Disease Group 3 Experimental Treatment 1 Intervention

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with gastric, Gastro Esophageal Junction (GEJ), and esophageal adenocarcinomas will enroll in this group.

Group XIX: Phase 1b: Dose Expansion Cohort Disease Group 2 Experimental Treatment 1 Intervention

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with Endometrial/Uterine cancer will enroll in this group.

Group XX: Phase 1b: Dose Expansion Cohort Disease Group 1 Experimental Treatment 1 Intervention

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) will enroll in this group.

Group XXI: Phase 1a Dose Escalation Experimental Treatment 1 Intervention

INCB123667 will be administered at a protocol defined starting regimen once daily (QD) orally in 28-day cycles. Subsequent dose regimens will be determined during study conduct.

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

mTOR dysregulation is a common feature in many tumors, leading to challenges in cancer treatment due to drug resistance and altered signaling pathways.

It is crucial to assess mTOR activity profiles in patients before using mTOR inhibitors, as first-generation inhibitors may not work effectively if mTORC2 is hyperactive; ongoing trials of new inhibitors show promise for advanced-stage patients selected based on molecular markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[he importance of mTOR hyperactivity and RICTOR amplification, and the associated targeted therapy possibilities in malignant tumours]. Szalai, F., Krencz, I., Moldvai, D., et al.[2023]

mTOR inhibitors, such as temsirolimus, are important in cancer treatment as they target dysregulated pathways involved in cell growth and proliferation, with temsirolimus being specifically approved for solid tumors.

Research is ongoing to better understand mTOR pathways and their role in various cancers, with studies exploring mTOR inhibition both as a standalone treatment and in combination with other therapies to combat drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NCCN Task Force Report: mTOR inhibition in solid tumors. Figlin, RA., Brown, E., Armstrong, AJ., et al.[2021]

In a study of 435 cancer patients, RICTOR overexpression was found in 49% of solid tumors, indicating its potential role in promoting cancer cell proliferation and survival.

Immunohistochemistry (IHC) can effectively screen for RICTOR amplification, which was detected in 75.7% of IHC-positive cases, suggesting that IHC may be a valuable diagnostic tool for identifying tumors with RICTOR alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation between RICTOR overexpression and amplification in advanced solid tumors. Bang, H., Ahn, S., Ji Kim, E., et al.[2020]

mTOR inhibitors like temsirolimus and everolimus have been shown to be effective in treating advanced renal cell carcinoma (RCC), with temsirolimus being FDA-approved for this use.

These inhibitors are also being evaluated for their potential effectiveness against various other cancer types, including breast cancer and leukemia, indicating their broad therapeutic potential in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. Yuan, R., Kay, A., Berg, WJ., et al.[2023]

In a study of eight breast cancer cell lines, six were sensitive to the mTOR inhibitor CCI-779, particularly those that were estrogen-dependent or lacked the tumor suppressor PTEN, indicating that mTOR is a promising target for treatment in these cases.

In mouse models, CCI-779 effectively inhibited the growth of sensitive tumors but not resistant ones, suggesting that the presence of certain molecular characteristics, like PTEN loss or Her-2/neu overexpression, can predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Yu, K., Toral-Barza, L., Discafani, C., et al.[2021]

References

1. Hungary pubmed.ncbi.nlm.nih.gov

[he importance of mTOR hyperactivity and RICTOR amplification, and the associated targeted therapy possibilities in malignant tumours]. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

NCCN Task Force Report: mTOR inhibition in solid tumors. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Correlation between RICTOR overexpression and amplification in advanced solid tumors. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. [2023]

5. England pubmed.ncbi.nlm.nih.gov

mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. [2021]