JDQ443 Combinations for Advanced Cancer

(KontRASt-03 Trial)

Recruiting at 15 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Brain metastases, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

74 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What makes the drug JDQ443 unique for advanced cancer treatment?

JDQ443, also known as Opnurasib, is unique because it is being studied in combination with other therapies to potentially enhance its effectiveness against advanced cancer, which may offer new options for patients who have not responded to standard treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests JDQ443, a new drug, combined with other treatments for patients with advanced cancers having the KRAS G12C mutation. The drug aims to stop cancer growth by targeting a specific genetic fault.

Eligibility Criteria

This trial is for adults with advanced solid tumors that have a specific mutation called KRAS G12C. It's open to those who've had standard treatments or can't receive them, and they should be able to undergo a tumor biopsy. People with poor organ function, active brain metastases, significant heart issues, or prior treatment with KRAS G12C inhibitors (in some cases) are excluded.

Inclusion Criteria

I have advanced colorectal cancer with a specific mutation and have been treated with certain chemotherapies.

I can have a biopsy based on my hospital's rules.

I have advanced lung cancer with a specific mutation and have had platinum chemotherapy and immunotherapy.

Exclusion Criteria

I have not taken a KRAS G12C inhibitor for my condition.

My liver, kidneys, or bone marrow are not working well.

I have active brain cancer spread.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive JDQ443 in combination with selected therapies to determine the maximum tolerated dose and safety

24 months

Phase II

Further exploration of safety, tolerability, and anti-tumor activity of JDQ443 combinations

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cetuximab
• JDQ443
• Ribociclib
• Trametinib

Trial Overview The study is testing JDQ443 in combination with other drugs like trametinib, ribociclib, and cetuximab on patients whose tumors have the KRAS G12C mutation. This adaptive platform study will adjust based on results as it progresses through phases Ib/II.

Participant Groups

Group I: JDQ443+trametinib Experimental Treatment 2 Interventions

JDQ443 in combination with trametinib

Group II: JDQ443+ribociclib Experimental Treatment 2 Interventions

JDQ443 in combination with ribociclib

Group III: JDQ443+cetuximab Experimental Treatment 2 Interventions

JDQ443 in combination with cetuximab

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

In a clinical trial involving 55 patients with advanced solid tumors, the PD-1 inhibitor dostarlimab was found to be well tolerated in both doublet and triplet combination therapies, with no new safety concerns arising.

The triplet combinations showed higher disease control rates compared to doublets, with preliminary antitumor activity observed in various combinations, indicating potential for improved efficacy in treating advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab in patients with advanced cancer. Yap, TA., Bessudo, A., Hamilton, E., et al.[2022]

The combination of olaparib, cediranib, and durvalumab was found to be tolerable in a phase 1 study involving 9 patients with recurrent women's cancers, with no dose-limiting toxicities reported.

The treatment showed promising preliminary efficacy, with a 67% clinical benefit rate, including partial responses in 44% of patients, indicating potential for further investigation in a phase 2 study for recurrent ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1-3 inhibitor, cediranib, in recurrent women's cancers with biomarker analyses. Zimmer, AS., Nichols, E., Cimino-Mathews, A., et al.[2023]

In the PENELOPE trial, adding pertuzumab to chemotherapy (either topotecan or paclitaxel) showed a median progression-free survival of about 4.1 to 4.2 months in patients with platinum-resistant ovarian cancer and low HER3 expression, indicating potential efficacy in this specific subgroup.

The treatment was generally well-tolerated, although common adverse events included fatigue, anemia, and neutropenia, with some serious adverse events leading to patient deaths, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab Plus Chemotherapy for Platinum-Resistant Ovarian Cancer: Safety Run-in Results of the PENELOPE Trial. González-Martín, A., Pautier, P., Mahner, S., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Anlotinib combined with anti-PD-1 antibody, camrelizumab for advanced NSCLCs after multiple lines treatment: An open-label, dose escalation and expansion study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Lessons learned from the blockade of immune checkpoints in cancer immunotherapy. [2022]

3. England pubmed.ncbi.nlm.nih.gov

IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab in patients with advanced cancer. [2022]

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

A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1-3 inhibitor, cediranib, in recurrent women's cancers with biomarker analyses. [2023]

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

Pertuzumab Plus Chemotherapy for Platinum-Resistant Ovarian Cancer: Safety Run-in Results of the PENELOPE Trial. [2022]