Divarasib vs Other Treatments for Lung Cancer

(Krascendo 1 Trial)

Recruiting at 269 trial locations

Overseen By Reference Study ID Number: BO45217 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: KRAS inhibitors

Disqualifiers: CNS metastases, Leptomeningeal disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 4 years

320 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, divarasib, against other medicines for a specific type of advanced lung cancer, known as KRAS G12C-positive non-small cell lung cancer (NSCLC). Researchers aim to determine if divarasib is safe and effective compared to existing treatments like sotorasib and adagrasib. The trial may suit those with this type of lung cancer who have already tried other treatments but need another option. Participants must have a confirmed KRAS G12C mutation in their cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to a potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

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

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

Research shows that divarasib, a treatment under study for lung cancer, generally has a manageable safety profile. Side effects were usually mild and easily handled by patients, with most experiencing no severe problems.

More information is available for sotorasib and adagrasib. The FDA has approved both for treating certain types of lung cancer, indicating their safety for many people. Common side effects include diarrhea and fatigue, but these are usually mild and manageable.

Overall, studies suggest these treatments are generally safe, with side effects that are not too severe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Divarasib is unique because it targets a specific mutation in lung cancer, the KRAS G12C mutation, which is a common and challenging mutation to treat. Unlike standard treatments like chemotherapy, Divarasib is designed to block the mutant KRAS protein, potentially stopping cancer growth more effectively. Researchers are excited about Divarasib as it offers a new way to directly target this mutation with a once-daily oral medication, which could mean fewer side effects and more convenience for patients compared to traditional therapies.

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

Research shows that divarasib, one of the treatments studied in this trial, holds promise for treating KRAS G12C-positive non-small cell lung cancer (NSCLC). Studies have shown that about 53.4% of patients with this cancer type responded well to divarasib, meaning their cancer shrank or disappeared. In this trial, participants may receive divarasib or other drugs like sotorasib and adagrasib, which also target the KRAS G12C mutation and effectively treat this condition. Divarasib works similarly by targeting the KRAS G12C mutation, common in some lung cancers, to halt tumor growth. Overall, these treatments aim to target specific cancer mutations, offering hope for better management of this challenging cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for people with advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific mutation known as KRAS G12C. Participants should have previously been treated for their condition.

Inclusion Criteria

My cancer has a KRAS G12C mutation.

My cancer has worsened despite 1-3 treatments.

Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Exclusion Criteria

Known hypersensitivity to any of the components of divarasib, sotorasib, or adagrasib

I do not have conditions that affect how my body absorbs food.

I have pain from my cancer that isn't relieved by treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive divarasib or a KRAS G12C inhibitor (sotorasib or adagrasib) orally

Up to approximately 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adagrasib
• Divarasib
• Sotorasib

Trial Overview The study is testing the effectiveness and safety of a new drug called Divarasib compared to already approved drugs, Sotorasib or Adagrasib, in patients with the KRAS G12C mutation in NSCLC.

How Is the Trial Designed?

Group I: Divarasib Experimental Treatment 1 Intervention

Participants will receive divarasib orally, once daily (QD).

Group II: KRAS G12C inhibitor Active Control 2 Interventions

Participants will receive sotorasib orally QD or adagrasib orally twice a day (BID)

Adagrasib is already approved in United States, European Union for the following indications:

Approved in United States as Krazati for:

• KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)
• KRAS G12C-mutated locally advanced or metastatic colorectal cancer

Approved in European Union as Krazati for:

• KRAS G12C mutation non-small cell lung cancer

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Chugai Pharmaceutical

Industry Sponsor

Trials

105

Recruited

25,000+

Dr. Osamu Okuda

Chugai Pharmaceutical

Chief Executive Officer since 2020

MD from Kyoto University

Dr. Mariko Y. Momoi

Chugai Pharmaceutical

Chief Medical Officer

MD from Jichi Medical University

Published Research Related to This Trial

Sotorasib and adagrasib, both KRAS G12C-targeting agents, have shown promising efficacy in treating non-small cell lung cancer (NSCLC), with sotorasib achieving an overall response rate of 41% and a progression-free survival of 6.3 months, while adagrasib had an overall response rate of 42.9% and a progression-free survival of 6.5 months.

Both drugs have received accelerated FDA approval and are now recommended as second-line treatment options for patients with KRAS G12C-mutated NSCLC, although they come with common side effects like diarrhea and fatigue, highlighting the need for further studies to refine their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapies for Previously "Undruggable" KRAS-Mutated Non-Small Cell Lung Cancer: A Review of Sotorasib and Adagrasib. Mausey, N., Halford, Z.[2023]

In the phase I/II CodeBreaK100 trial, the KRASG12C inhibitor sotorasib demonstrated a 21.1% objective response rate in patients with pancreatic ductal adenocarcinoma who had previously undergone at least one therapy.

Additionally, sotorasib achieved an impressive 84.2% disease control rate, indicating its potential effectiveness in managing this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib Tackles KRASG12C-Mutated Pancreatic Cancer. [2022]

Adagrasib combined with pembrolizumab shows promising efficacy for patients with newly diagnosed non-small cell lung cancer with a KRASG12C mutation, achieving overall response rates of 49% and 57% in two separate trials.

This drug combination demonstrated a favorable safety profile, exhibiting lower liver toxicity compared to other combinations of checkpoint inhibitors and targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

In the phase II KRYSTAL-1 trial, the KRASG12C inhibitor adagrasib demonstrated a 43% overall response rate and an 80% disease control rate in patients with previously treated KRASG12C-mutant non-small cell lung cancer, indicating its efficacy in this specific cancer type.

Patients treated with adagrasib had a median overall survival of 11.7 months, and the drug was effective in reducing brain metastases in 33% of patients with such conditions, highlighting its potential for managing advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adagrasib Response Remains Strong in NSCLC. [2022]

Sotorasib is the first commercially available KRASG12C inhibitor, showing promise in improving outcomes for patients with KRASG12C-mutated non-small cell lung cancer (NSCLC), which is prevalent among smokers.

Despite its potential, there are ongoing questions about sotorasib's effectiveness in the brain, optimal dosing, and how it compares to standard treatments, highlighting the need for further research on resistance mechanisms and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. Strohbehn, GW., Sankar, K., Qin, A., et al.[2022]

Sotorasib is a first-in-class oral medication that specifically targets the KRAS G12C mutation in non-small cell lung cancer (NSCLC), showing a clinically relevant objective response rate in patients during the CodeBreaK 100 trial.

The drug has a manageable safety profile, allowing for dose adjustments to handle any side effects, making it a valuable treatment option for patients with advanced KRAS G12C mutation-positive NSCLC who have already undergone other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. Lee, A.[2022]

Sotorasib (Lumakras) received accelerated FDA approval for treating advanced non-small cell lung cancer (NSCLC) with a KRAS G12C mutation, showing an overall response rate of 36% in a study of 124 patients.

The median duration of response to sotorasib was 10 months, with common side effects including diarrhea, musculoskeletal pain, and nausea, highlighting its efficacy and safety profile as a targeted therapy for this specific cancer mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC. Nakajima, EC., Drezner, N., Li, X., et al.[2022]

Adagrasib demonstrates durable efficacy in patients with advanced KRASG12C non-small cell lung cancer, with about one in three patients surviving after 2 years of treatment.

The long-term safety profile of adagrasib remains manageable, as no new toxicities were reported during the study, indicating it is a safe option for previously treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adagrasib's Efficacy Sustained in KRASG12C NSCLC. [2023]

The KRYSTAL-1 study found that adagrasib (MRTX849), a KRASG12c inhibitor, is generally well tolerated by patients with non-small cell lung cancer, indicating a favorable safety profile.

Adagrasib demonstrated significant efficacy in treating non-small cell lung cancer with the KRASG12c mutation, and it also showed some activity in colorectal cancer and other solid tumors, although to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Another KRAS Inhibitor Holds Its Own. [2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00040

Single-Agent Divarasib in Patients With <i>KRAS G12C</i> Divarasib (GDC-6036), an oral, highly potent and selective next-generation KRAS G12C inhibitor, has demonstrated a manageable safety profile and promising ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303810

Single-Agent Divarasib (GDC-6036) in Solid Tumors with a ... Among patients with NSCLC, a confirmed response was observed in 53.4% of patients (95% confidence interval [CI], 39.9 to 66.7), and the median ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11111488/

Divarasib in the Evolving Landscape of KRAS G12C Inhibitors ... Within the NSCLC cohort, investigators reported an objective response rate (ORR) of 53.4% (95% CI 39.9–66.7) with a median progression-free ...

4. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/lung-cancer/a-study-evaluating-the-efficacy-and-safety-of-divarasib-53110.html

Clinical trial for Non Small Cell Lung Carcinoma-Genentec... This study is testing a combination of medicines called divarasib plus pembrolizumab. It is being developed to treat previously untreated NSCLC that has spread.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06793215

NCT06793215 | A Study Evaluating the Efficacy and Safety ... The purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40632992/

Single-Agent Divarasib in Patients With KRAS G12C- ... Divarasib (GDC-6036), an oral, highly potent and selective next-generation KRAS G12C inhibitor, has demonstrated a manageable safety profile and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05789082

NCT05789082 | A Study Evaluating the Safety, Activity, and ... The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of divarasib combined with other anti-cancer therapies in participants ...

8. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT022/761573/Abstract-CT022-Divarasib-plus-migoprotafib

Divarasib plus migoprotafib combination treatment in patients ... Divarasib plus migoprotafib combination treatment in patients with KRAS G12C-positive non-small cell lung cancer (NSCLC)