JDQ443 Combinations for Advanced Cancer

(KontRASt-03 Trial)

Not currently recruiting at 18 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called JDQ443, combined with other drugs, for people with advanced solid tumors that have a specific genetic change known as the KRAS G12C mutation. Researchers aim to evaluate the effectiveness of these combinations against cancers that have spread or cannot be surgically removed, particularly in lung and colorectal cancer. The trial includes different groups testing JDQ443 with trametinib, ribociclib, or cetuximab. Suitable candidates are those with these specific cancers who have not responded to certain standard treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that JDQ443 appears safe when combined with other treatments for advanced cancers. Early results for the combination of JDQ443 and trametinib indicate it may shrink tumors in some cancers with the KRAS G12C mutation, suggesting it might be well-tolerated, though specific safety details are not provided.

Similarly, the combination of JDQ443 and ribociclib is under safety testing in patients with advanced tumors. While detailed safety results are unavailable, its study in multiple trials suggests it is tolerable enough to continue testing.

JDQ443 combined with cetuximab targets the KRAS G12C mutation, offering a focused approach to attacking cancer cells. Although specific safety information is not highlighted, ongoing research supports its potential acceptability for patients.

As this study is in Phases 1 and 2, it remains early in the testing process. Researchers closely monitor patient tolerance and any side effects. This phase aims to ensure the treatment is safe enough for larger trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about JDQ443 combinations for advanced cancer because they offer a novel approach to treatment. Unlike traditional therapies that often target cancer cells broadly, JDQ443 is designed to work in combination with other drugs, like trametinib, ribociclib, and cetuximab, to specifically target cancer cell pathways. This targeted approach may improve effectiveness and reduce side effects compared to standard care options. Additionally, the combination with different drugs allows for a personalized treatment strategy, potentially offering better outcomes for patients with advanced cancer.

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

Research has shown that JDQ443 may help treat advanced solid tumors with the KRAS G12C mutation. In this trial, participants will receive JDQ443 alongside other treatments. One arm will test JDQ443 with trametinib, which effectively targets the KRAS mutation, often driving certain cancers. Another arm will evaluate JDQ443 combined with ribociclib, which has shown promise in treating these mutations. Additionally, JDQ443 with cetuximab will be tested in a separate arm, with early research indicating positive results. These findings suggest JDQ443 could be a valuable treatment option for people with this specific genetic mutation in their cancer. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05358249

NCT05358249 | Platform Study of JDQ443 in ... This is Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select therapies in patients with advanced solid tumors harboring the KRAS ...

2. tandfonline.com tandfonline.com/doi/full/10.1080/14656566.2025.2536352?src=

Profiling opnurasib (JDQ-443) for the treatment of non- ... Despite promising safety and efficacy outcomes and ongoing innovative trials, development of JDQ-443 has been terminated, highlighting critical challenges ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9394399/

Discovery, Preclinical Characterization, and Early Clinical ... We present the in vitro and in vivo efficacy of JDQ443 both alone and in combination with inhibitors of RAS upstream and downstream signaling components.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11575457/

The Potential Treatment Options and Combination Strategies ... These results affirm JDQ-443's reliability and efficacy for treating NSCLC patients with KRAS exon 2 p.G12C mutations. Other KRAS Exon 2 P. G12C ...

5. veri.larvol.com veri.larvol.com/news/jdq443/drug

News - opnurasib (JDQ443) Study of efficacy and safety of JDQ443 single-agent as first-line treatment for patients with locally advanced or metastatic KRAS G12C- mutated non-small cell ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05358249

NCT05358249 | Platform Study of JDQ443 in ... This is Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select therapies in patients with advanced solid tumors harboring the KRAS ...

7. clinicaltrial.be clinicaltrial.be/en/details/28683?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Platform Study of JDQ443 in Combinations in Patients With... Discover the latest clinical trials, research studies, and groundbreaking medical advances with our comprehensive, user-friendly platform.