Sotorasib + Trastuzumab Deruxtecan for Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

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

Disqualifiers: Interstitial lung disease, Severe pulmonary compromise, Major surgery, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 5

Duration: 21 days per cycle

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for KRAS G12C mutated non-small cell lung cancer. It evaluates the safety and effectiveness of combining two drugs, sotorasib and trastuzumab deruxtecan, for this condition. Sotorasib blocks a protein that promotes cancer growth, while trastuzumab deruxtecan targets another protein and delivers chemotherapy directly to cancer cells. Individuals previously treated for lung cancer with specific therapies and possessing a particular genetic mutation might be suitable for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking strong CYP3A4 inducers, you should switch to an alternative drug. Also, avoid taking P-glycoprotein substrates that could lead to serious toxicities.

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

Research shows that combining sotorasib and trastuzumab deruxtecan holds promise for treating certain lung cancers. Patients generally tolerate this combination well. Sotorasib targets a protein that aids cancer growth, while trastuzumab deruxtecan delivers chemotherapy directly to cancer cells.

Reports indicate that side effects can vary. Some patients experience mild to moderate side effects, but these are usually manageable. Sotorasib already has FDA approval for another type of cancer, suggesting its relative safety. Similarly, trastuzumab deruxtecan is used in other approved treatments.

While the trial is ongoing, current data provides reassurance about the treatment's safety. However, individual experiences may differ, so discussing this with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Sotorasib and Trastuzumab Deruxtecan for lung cancer because these treatments bring a novel approach to tackling the disease. Sotorasib targets a specific mutation in the KRAS gene, which is a common driver in various cancers but has been notoriously difficult to treat effectively. Trastuzumab Deruxtecan is an antibody-drug conjugate, meaning it delivers targeted chemotherapy directly to the cancer cells, potentially increasing effectiveness while minimizing damage to healthy cells. This combination could offer a more effective and precise treatment option compared to traditional chemotherapy and other current standards of care.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that sotorasib effectively treats non-small cell lung cancer with the KRAS G12C mutation. It shrinks tumors in about one-third of patients, with a response rate between 28% and 37%. Patients experience a progression-free survival period of about 5.6 to 6.8 months, during which the cancer does not worsen.

Trastuzumab deruxtecan is another promising treatment. It delivers chemotherapy directly to cancer cells with the HER2 marker, enhancing treatment effectiveness. This trial will evaluate the combination of trastuzumab deruxtecan and sotorasib, as early studies suggest this combination may improve outcomes for patients, even in advanced cancer stages. ^{1 2 3 6 7}

Who Is on the Research Team?

Bruna Pellini Ferreira

Principal Investigator

University Health Network Princess Margaret Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced or metastatic non-small cell lung cancer that has a KRAS G12C mutation. They must have been previously treated with both a KRAS G12C inhibitor and an immune checkpoint inhibitor or chemotherapy. Participants need documented HER2 status, measurable disease by CT/MRI, and specific blood health levels.

Inclusion Criteria

My advanced lung cancer has a specific mutation and was treated with targeted therapy and immunotherapy or chemotherapy.

I have records of my previous KRAS^G12C inhibitor treatment, including the type and dates.

I have records of my last KRASG12C inhibitor dose and when my disease worsened.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 and sotorasib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months for up to 5 years.

Up to 5 years

Every 3 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Sotorasib
• Trastuzumab Deruxtecan

Trial Overview The trial is testing the combination of sotorasib (a targeted therapy blocking mutated KRAS protein) and trastuzumab deruxtecan (an antibody-drug conjugate targeting HER2 positive cells) to see if they're safe together, what the best dose might be, and how effective they are against this type of lung cancer.

How Is the Trial Designed?

Group I: Treatment (trastuzumab deruxtecan, sotorasib) Experimental Treatment 8 Interventions

Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 and sotorasib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy and brain MRI at screening and ECHO or MUGA, CT, MRI and blood sample collection throughout the study. Additionally, patients with brain metastasis undergo brain MRI throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT07012031/sotorasib-in-combination-with-trastuzumab-deruxtecan-for-the-treatment-of-locally-advanced-and-metastatic-non-small-cell-lung-cancer-with-a-kras-g12c-mutation

Sotorasib in Combination With Trastuzumab Deruxtecan ... This phase I/II trial tests the safety, side effects and best dose of sotorasib with trastuzumab deruxtecan and how well the combination ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39764052/

Trastuzumab Deruxtecan Combination Strongly Enhances ... Conclusions: Our results support the potential clinical utility of the sotorasib-T-DXd combination, including tumors with intrinsic and acquired ...

3. biorxiv.org biorxiv.org/content/10.1101/2024.12.17.628751v1

Trastuzumab Deruxtecan Combination Strongly Enhances ... In this study, we investigated the therapeutic potential of combining trastuzumab deruxtecan (T-DXd), an anti-HER2 antibody-drug conjugate, with sotorasib in ...

4. patlynk.com patlynk.com/trial/NCT07012031

Sotorasib Plus Trastuzumab Deruxtecan for Advanced ... This clinical trial is focused on understanding the safety and effectiveness of combining two drugs, sotorasib and trastuzumab deruxtecan, for patients with ...

5. ascopubs.org ascopubs.org/doi/10.1200/PO.22.00621

Mutant Non–Small-Cell Lung Cancer Sotorasib is the first approved drug for metastatic KRAS G12C-mutant NSCLC, with a response rate of 28%-37% and median progression-free survival of 5.6-6.8 ...

6. biorxiv.org biorxiv.org/content/10.1101/2024.12.17.628751v1.full.pdf

Sotorasib Resistance in KRASG12C-Mutant NSCLC Safety, Tolerability, and Efficacy of Sotorasib Plus Trastuzumab ... Trastuzumab Deruxtecan in HER2-Mutant Non-Small-. 678. Cell Lung Cancer.

7. app.trialscreen.org app.trialscreen.org/trials/phase-1-2-sotorasib-combination-trastuzumab-deruxtecan-treatment-locally-trial-nct07012031

Sotorasib in Combination With Trastuzumab Deruxtecan ... Benefits: Potential benefits include shrinking or slowing the growth of the cancer, and prolonging survival. Participation in this study may also contribute to ...