Divarasib + Pembrolizumab for Lung Cancer

(Krascendo 2 Trial)

Recruiting at 150 trial locations

Overseen By Reference Study ID Number: CO45042 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Immunostimulants, QT-prolonging drugs, Antibiotics

Disqualifiers: CNS metastases, Prior cancer therapy, 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

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 5 years

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two treatments, divarasib (a new potential drug) and pembrolizumab (an immunotherapy), for people with advanced lung cancer. It focuses on a specific type of lung cancer with a KRAS G12C mutation, which influences cell growth. Participants will receive either the new combination of divarasib and pembrolizumab or the standard treatment of pembrolizumab and chemotherapy drugs. The trial seeks participants who have not previously received treatment for their advanced lung cancer and have a confirmed KRAS G12C mutation. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial requires that you stop any anti-cancer systemic therapy, including hormonal therapy, at least 21 days before joining. You also cannot be on medications that prolong the QT interval or on systemic immunosuppressive or immunostimulatory medications. If you're on antibiotics, you need to stop them 2 weeks before joining.

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

Research shows that divarasib, when combined with pembrolizumab, has undergone safety testing in people with certain types of lung cancer. In earlier studies, patients with a specific mutation called KRAS G12C received divarasib, which was generally well-tolerated. Some participants experienced side effects, but these were mostly manageable.

Pembrolizumab alone has FDA approval for treating lung cancer and is considered safe for many, though it can cause side effects like tiredness and skin reactions.

Both treatments have been tested in previous trials, demonstrating sufficient safety in humans for continued research. However, like any medical treatment, risks exist, so discussing expectations with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Divarasib and Pembrolizumab for lung cancer because it targets cancer in a unique way. Unlike standard treatments like chemotherapy, which attack fast-growing cells broadly, Divarasib specifically inhibits a protein involved in cancer cell growth, potentially leading to fewer side effects. Additionally, Pembrolizumab is an immunotherapy that helps the immune system recognize and fight cancer cells more effectively. This combination could offer a more precise attack on cancer cells, possibly improving outcomes for patients.

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

This trial will compare two treatment combinations for lung cancer. Studies have shown that divarasib, one of the treatments in this trial, helps patients with a specific type of lung cancer live without disease progression for about 13.8 months on average when used alone. This finding suggests that divarasib may effectively slow cancer. Divarasib is a targeted treatment that specifically attacks a common mutation in certain lung cancers. Pembrolizumab, the other drug in the divarasib combination arm, is an immunotherapy that boosts the body's natural defenses to fight cancer. Early research suggests that using these two treatments together may improve outcomes for patients with this type of lung cancer. ^{4 6 7 8 9}

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 adults with advanced or metastatic non-squamous NSCLC who haven't had systemic treatment before. They must have a specific KRAS G12C mutation, measurable disease, and be in good enough health to handle platinum-based chemotherapy. A tumor sample and PD-L1 status are also required.

Inclusion Criteria

I can be treated with platinum-based chemotherapy.

Measurable disease, as defined by RECIST v1.1

My cancer's PD-L1 status is documented.

Exclusion Criteria

I am not taking any medications known to affect heart rhythm.

I have had cancer spread to the lining of my brain and spinal cord.

I have been treated with KRAS G12C or pan-KRAS/RAS inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive divarasib and pembrolizumab or pembrolizumab, pemetrexed, and carboplatin or cisplatin

Up to approximately 5 years

Every 3 weeks (Q3W) for IV infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Divarasib
• Pembrolizumab

Trial Overview

The study compares the effectiveness of Divarasib plus Pembrolizumab against Pembrolizumab combined with Pemetrexed and either Carboplatin or Cisplatin in first-line treatment for certain lung cancer patients. It aims to see which combination works better.

How Is the Trial Designed?

Group I: Divarasib + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive divarasib orally, once daily (QD) and pembrolizumab via intravenous (IV) infusion every 3 weeks (Q3W)

Group II: Pembrolizumab + Pemetrexed + Carboplatin or Cisplatin Active Control 4 Interventions

Participants will receive pembrolizumab, pemetrexed and carboplatin or cisplatin via IV infusion Q3W

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

Citations

1.

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 ...

2.

ascopubs.org

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

Single-Agent Divarasib in Patients With <i>KRAS G12C</i>

The median progression-free survival was 13.8 months (95% CI, 9.8 to 25.4) in the overall population (N = 65) and 15.3 months (95% CI, 12.3 to ...

3.

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 aims to compare the effects of divarasib plus pembrolizumab versus standard first treatment (pembrolizumab plus chemotherapy) in people with NSCLC ...

4.

forpatients.roche.com

forpatients.roche.com/content/patient-platform/global/en/trials/cancer/lung-cancer/a-study-evaluating-the-efficacy-and-safety-of-divarasib-53110.pdf

A study to compare divarasib plus pembrolizumab with standard

The purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or.

5.

humanforschung-schweiz.ch

humanforschung-schweiz.ch/de/studiensuche/studien-detail/67300/translate/en/?cHash=9cc81656e7995c1c1a9d32d350d306b3

A Study Comparing Divarasib plus Pembrolizumab with ...

Divarasib is a targeted therapy that may work well in non-small cell lung cancer with a KRAS-G12C mutation. It is still a drug in the testing ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12527784/

Single-Agent Divarasib in Patients With KRAS G12C ...

Overall, 65 patients with advanced KRAS G12C–positive NSCLC received single-agent oral divarasib 50-400 mg once daily and 31 patients (48%) were ...

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.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS8651

Krascendo-170 Lung: A phase Ib/II study of divarasib + ...

A phase Ib/II, open-label study evaluating the safety and activity of divarasib + pembrolizumab in patients with PD-L1 tumor cell expression ≥1%.

9.

forpatients.roche.com

forpatients.roche.com/content/patient-platform/global/en/trials/cancer/lung-cancer/a-study-evaluating-the-safety--activity--and-pharmacoki-06656.pdf

A clinical trial to look at the safety and activity of divarasib at

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