What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies, immunotherapies, and chemotherapy. Targeted therapies, such as those inhibiting specific mutations like KRAS G12C, can cause side effects including diarrhea, liver enzyme abnormalities, and skin rash. Immunotherapies, like pembrolizumab and durvalumab, often lead to immune-related adverse events such as pneumonitis, colitis, hepatitis, and endocrinopathies. Chemotherapy, using agents like carboplatin and paclitaxel, is associated with side effects such as nausea, vomiting, hair loss, fatigue, and increased risk of infection due to bone marrow suppression.

What prior FDA approvals exist?

Several FDA-approved treatments for Non-Small Cell Lung Cancer (NSCLC) target specific molecular pathways. For instance, pembrolizumab, an anti-PD-1 therapy, has been approved for use in combination with chemotherapy for advanced NSCLC, showing improved overall survival and progression-free survival. Additionally, fam-trastuzumab deruxtecan, an antibody-drug conjugate, is approved for patients with HER2-mutant NSCLC. These treatments, like the investigational agent Divarasib, aim to target specific genetic mutations or pathways to improve patient outcomes.

What other types of research exist?

Promising novel alternatives to Divarasib for NSCLC patients include: 1) Sotorasib, which targets the KRAS p.G12C mutation and has shown durable clinical benefits in previously treated patients. 2) Gefitinib (IRESSA), particularly effective in patients of Asian origin and those who have never smoked. 3) Dacomitinib, which has shown efficacy in patients with rare EGFR mutations like delE709_T710insD. These therapies offer targeted approaches based on specific genetic mutations and have demonstrated clinical efficacy in trials.

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Small Molecule Drug

Divarasib + Pembrolizumab for Non-Small Cell Lung Cancer (Krascendo 170 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called divarasib along with other cancer treatments. It focuses on people with advanced or metastatic non-small cell lung cancer. The study aims to see how divarasib moves through the body, its safety, and if it helps fight the cancer.

Who is the study for?

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) that hasn't been treated yet and has a specific mutation called KRAS G12C. Participants need to have measurable disease, be in good physical condition (ECOG 0 or 1), and provide tumor tissue samples. They can't join if they've had another cancer within the last 5 years, untreated brain metastases, uncontrolled symptoms from their cancer, prior treatment with KRAS G12C inhibitors, certain lung conditions, active infections like TB, or recent heart problems.

What is being tested?

The study tests Divarasib combined with other anti-cancer drugs: Pemetrexed, Cisplatin/Carboplatin and Pembrolizumab in patients who haven’t received any previous treatments for their NSCLC. It aims to assess how safe this combination is and how it affects the body (pharmacokinetics) as well as its effectiveness against the cancer.

What are the potential side effects?

Possible side effects include reactions related to immune system activation such as inflammation of organs; infusion-related reactions; fatigue; nausea; blood count changes which could lead to increased infection risk; kidney function changes due to chemotherapy agents like Cisplatin/Carboplatin.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Duration of Response (DOR)

Identification of Divarasib Recommended Dose

Objective Response Rate (ORR)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohort B - Combination Dose Finding + Dose ExpansionExperimental Treatment5 Interventions

Participants enrolled in this cohort will receive divarasib (different dose levels will be evaluated) QD combined with pembrolizumab 200 mg IV Q3W plus investigator's choice of platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed.

Group II: Cohort A - Combination Dose Finding + Dose ExpansionExperimental Treatment2 Interventions

Participants enrolled in this cohort will receive divarasib (different dose levels will be evaluated) once a day (QD) combined with pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W). During the expansion stage, some participants are planned to be randomized to one divarasib combination dose level; other participants are planned to be randomized to another divarasib combination dose level. Divarasib will be given in combination with pembrolizumab.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Divarasib

2021

Completed Phase 1

~430

Carboplatin

2014

Completed Phase 3

~6120

Cisplatin

2013

Completed Phase 3

~3120

Pemetrexed

2014

Completed Phase 3

~5550

Pembrolizumab

2017

Completed Phase 3

~3130

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies, immunotherapies, and chemotherapy. Targeted therapies, such as those inhibiting KRAS G12C mutations (e.g., sotorasib and adagrasib), work by specifically blocking the molecular pathways that drive cancer cell growth and survival. Immunotherapies, like pembrolizumab, enhance the body's immune response against cancer cells by targeting immune checkpoints. Chemotherapy, using agents like cisplatin and paclitaxel, kills rapidly dividing cells, including cancer cells, but also affects normal cells. These treatments are crucial for NSCLC patients as they offer personalized and effective options, especially for those with specific genetic mutations, leading to better outcomes and potentially fewer side effects compared to traditional chemotherapy.

Emerging therapeutic agents for lung cancer.