Targeted Therapy for Lung Cancer

(B-FAST Trial)

Not currently recruiting at 301 trial locations

Overseen By Reference Study ID Number: BO29554 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Hoffmann-La Roche

Disqualifiers: Pregnancy, Cns metastases, Cardiovascular, others

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

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: Varies by cohort, typically until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for advanced lung cancer that cannot be surgically removed. Researchers aim to evaluate the effectiveness of different drug combinations for individuals with specific gene mutations linked to their cancer. Participants should have advanced lung cancer that has not responded to other treatments and must have identified specific gene mutations through previous testing. As a Phase 2 trial, this research assesses the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to explore new treatment options.

Will I have to stop taking my current medications?

The trial information does not specify if 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 shows that the treatments in this trial have different safety profiles.

Alectinib is usually well-tolerated by patients with ALK-positive non-small cell lung cancer (NSCLC). Most side effects are mild, such as tiredness, constipation, and swelling, while serious side effects like liver problems are less common.

Atezolizumab, an immune system drug, can cause inflammation-related side effects, such as pneumonitis and liver issues, though these are rare.

Bevacizumab may lead to high blood pressure and bleeding, which are more serious but occur in fewer patients.

Carboplatin and cisplatin, chemotherapy drugs, often cause nausea, low blood cell counts, and kidney issues, with varying severity.

Cobimetinib, used for certain cancers, may cause diarrhea and skin issues but is generally well-tolerated.

Docetaxel, another chemotherapy drug, can lead to low blood counts and fluid retention, with side effects usually manageable.

Entrectinib, approved for ROS1-positive NSCLC, has a manageable safety profile with mild side effects like dizziness and taste changes.

GDC-6036 (Divarasib), a newer drug targeting KRAS mutations, has shown a manageable safety profile in early studies, though more data may be needed.

Gemcitabine, another chemotherapy drug for NSCLC, has mild side effects like nausea and low blood counts.

Pemetrexed can cause fatigue, nausea, and low blood cell counts, which are generally mild.

Vemurafenib targets specific cancer cell mutations, with common but usually mild side effects like joint pain and skin rash.

These treatments have been studied in various settings, showing mostly manageable side effects. However, individual experiences can vary. Always discuss concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they offer targeted approaches that differ from traditional chemotherapy. For example, GDC-6036 is a novel treatment that targets the KRAS G12C mutation, a specific genetic alteration found in some lung cancers, offering a more personalized approach compared to standard chemotherapy. Alectinib targets ALK-positive non-small cell lung cancer (NSCLC), providing an option with potentially fewer side effects and more specificity than traditional treatments like cisplatin or carboplatin. Another exciting option is the combination of atezolizumab, vemurafenib, and cobimetinib for BRAF V600 mutation, which integrates immunotherapy with targeted therapy to block cancer growth pathways and enhance the immune response. These innovations provide hope for more effective and tailored cancer treatment strategies.

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

In this trial, participants with non-small cell lung cancer (NSCLC) and specific KRAS mutations will receive either GDC-6036 or docetaxel. Previous studies have shown that GDC-6036 achieved a 53.4% confirmed positive response rate, with cancer not worsening for an average of 13.8 months. In comparison, docetaxel had a response rate of 24%, with cancer not worsening for about 3 months on average.

For participants with ALK-positive NSCLC, alectinib is being tested and has effectively slowed disease progression, significantly improving survival rates according to past research. Atezolizumab is another treatment option in this trial, known to extend the lives of patients with advanced or metastatic NSCLC. The combination of atezolizumab, vemurafenib, and cobimetinib is under study for its significant survival benefits in patients with specific mutations. Lastly, entrectinib is being evaluated for its effectiveness in ROS1-positive NSCLC, providing lasting responses and survival benefits as shown in previous studies. ^{6 7 8 9 10}

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-small cell lung cancer (NSCLC) who haven't had recent cancer treatments and are in fairly good health. They should be able to perform daily activities with ease to moderate difficulty, have a life expectancy of at least 12 weeks, and agree to use contraception.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

I have recovered from my last cancer treatment.

My organs are functioning well.

Exclusion Criteria

I have had cancer other than lung cancer in the last 5 years, but it was not likely to spread or be fatal.

I do not have serious heart issues like recent heart attacks or unstable angina.

I am HIV positive or have an AIDS-related illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive targeted therapies or immunotherapy as single agents or in combination based on their specific cohort assignment

Varies by cohort, typically until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Maintenance Therapy

Participants in certain cohorts may continue maintenance therapy until disease progression or unacceptable toxicity

Varies by cohort

What Are the Treatments Tested in This Trial?

Interventions

• Alectinib
• Atezolizumab
• Bevacizumab
• Carboplatin
• Cisplatin
• Cobimetinib
• Docetaxel
• Entrectinib
• GDC-6036
• Gemcitabine
• Pemetrexed
• Vemurafenib

Trial Overview The study tests various targeted therapies and immunotherapies—either alone or combined—for NSCLC. These include Alectinib, Atezolizumab, Pemetrexed, among others. The effectiveness of these treatments will be measured by their ability to shrink tumors or slow disease progression.

How Is the Trial Designed?

Group I: Cohort G: Divarasib or Docetaxel Experimental Treatment 2 Interventions

Experimental: Cohort G: GDC-6036 or Docetaxel This cohort includes participants with KRAS G12C mutation. Participants will receive GDC-6036 PO QD or IV docetaxel Q3W (75 mg/m\^2) until disease progression or unacceptable toxicity New participants will no longer receive docetaxel.

Group II: Cohort F: Atezolizumab, Bevacizumab, Carboplatin, and Pemetrexed Experimental Treatment 4 Interventions

This cohort includes participants with EGFR exon 20+ NSCLC. Participants will receive atezolizumab + bevacizumab + carboplatin + pemetrexed for 4 or 6 induction cycles (cycle = 21 days). After induction therapy, participants will continue maintenance treatment with atezolizumab + bevacizumab + pemetrexed until disease progression, unacceptable toxicity, withdrawal of consent, or death. Enrollment to Cohort F is complete.

Group III: Cohort E: Atezolizumab, Vemurafenib, and Cobimetinib Experimental Treatment 3 Interventions

This cohort includes participants with BRAF V600 mutation. Participants will receive: atezolizumab 1680 mg IV Q4W after the run-in period; cobimetinib 60 mg orally (PO) QD on Days 1-21 of each cycle during the run-in and triple-combination periods; and vemurafenib 960 mg PO twice daily (BID) on Days 1-21 of the initial run-in period, then 720 mg PO BID on Days 1-22 of the initial run-in period and on Days 1-28 of each cycle during the triple-combination period. Enrollment to Cohort E is complete.

Group IV: Cohort D: Entrectinib 600 Milligrams (mg) Experimental Treatment 1 Intervention

This cohort includes participants with c-ros oncogene 1 positive (ROS1+) NSCLC. Participants will receive entrectinib 600 mg orally once a day (QD) until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort D is complete.

Group V: Cohort C: Atezolizumab 1200 mg Experimental Treatment 1 Intervention

This cohort includes participants with bTMB positive NSCLC. Participants will receive atezolizumab at a dose of 1200 mg administered by IV infusion every 21 days (Q21D) until disease progression, loss of clinical benefit, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort C is complete.

Group VI: Cohort B: Dose Finding Phase (DFP) Alectinib Experimental Treatment 1 Intervention

This cohort includes participants with rearranged during transfection (RET) positive NSCLC. Participants may receive alectinib 900 or 1200 mg orally BID until disease progression, unacceptable toxicity, withdrawal of consent or death if the recommended phase 2 dose (RP2D) is not established in any other clinical study. Participants may receive 750 mg or 600 mg, if it is unsafe to pursue the higher starting dose. Enrollment to Cohort B is complete.

Group VII: Cohort B: Dose Expansion Phase (DEP) Alectinib Experimental Treatment 1 Intervention

This cohort includes participants with RET positive NSCLC. Participants will receive alectinib at the RP2D established in the DFP of Cohort B or a separate clinical study. Participants will continue receiving study treatment until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort B is complete.

Group VIII: Cohort A: Alectinib 600 Milligrams (mg) Experimental Treatment 1 Intervention

This cohort includes participants with anaplastic lymphoma kinase (ALK) positive NSCLC. Participants will receive alectinib 600 mg orally twice in a day (BID) until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort A is complete.

Group IX: Cohort C: Pemetrexed, Cisplatin or Carboplatin Active Control 3 Interventions

This cohort includes participants with bTMB positive, non-squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Carboplatin at a dose of area under the concentration-time curve (AUC) of 5 or 6 IV or cisplatin at a dose of 75 milligrams per meter square (mg/m\^2) IV on Day 1 of each cycle combined with pemetrexed at a dose of 500 mg/m\^2 IV on Day 1 of each cycle. Pemetrexed may be continued as maintenance therapy every 21 days (Q21D) as per local standard of care. Enrollment to Cohort C is complete.

Group X: Cohort Z: Natural History Cohort Active Control 1 Intervention

Participants with genomic profiles of interest that are not enrolled in the other cohorts will enter into natural history follow-up.

Group XI: Cohort C: Gemcitabine, Cisplatin or Carboplatin Active Control 3 Interventions

This cohort includes participants with bTMB positive, squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Gemcitabine 1250 mg/m\^2 IV on Days 1 and 8 of every cycle and cisplatin 75 mg/m\^2 IV on Day 1 Q21D or gemcitabine 1000 mg/m\^2 IV on Days 1 and 8 of every cycle and carboplatin AUC 5 IV on Day 1 Q21D. Enrollment to Cohort C is complete.

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

Approved in United States as Alecensa for:

• Metastatic ALK-positive non-small cell lung cancer (NSCLC)
• Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC

Approved in European Union as Alecensa for:

• Metastatic ALK-positive non-small cell lung cancer (NSCLC)
• Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC

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

Published Research Related to This Trial

Bevacizumab combined with cisplatin and gemcitabine (BCG) shows a favorable hazard ratio for progression-free survival compared to pemetrexed and cisplatin (PC) in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

BCG is more cost-effective than PC, with a lower monthly cost of 4,007 euros per patient and an incremental cost-effectiveness ratio of 34,919 euros per additional life-year gained, making it a viable first-line treatment option in Italy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of bevacizumab versus pemetrexed for advanced non-squamous NSCLC in Italy. Giuliani, G., Grossi, F., de Marinis, F., et al.[2022]

In a study of 170 patients with advanced non-small cell lung cancer, those treated with EGFR-TKIs as second-line therapy showed the highest response rate (36.1%) and the longest progression-free survival (PFS) of 9.31 months, compared to 15.0% response rate and 5.49 months PFS for docetaxel and 24.5% response rate and 5.42 months PFS for pemetrexed.

All three treatments (docetaxel, pemetrexed, and EGFR-TKIs) had comparable safety profiles, but there was no significant difference in median survival time (MST) among the groups, indicating that while EGFR-TKIs may offer better short-term benefits, long-term survival outcomes were similar across treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of docetaxol, pemetrexed and EGFR-TKIs as second-line treatment for patients with advanced non-small-cell lung cancer]. Zhang, RX., Cai, DY., Wu, XH., et al.[2018]

Lung cancer is the leading cause of cancer-related deaths in Europe and North America, with non-small cell lung cancer (NSCLC) making up 70-80% of cases, and current chemotherapy treatments show limited effectiveness with overall response rates below 20%.

The Southern Italy Cooperative Oncology Group is exploring new triplet chemotherapy combinations involving cisplatin and two additional agents, aiming to improve patient outcomes in advanced NSCLC, with ongoing phase I, II, and III trials evaluating the safety and efficacy of these new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any impact of new drugs on the outcome of advanced NSCLC? An overview of the Southern Italy Cooperative Oncology Group trials. Frasci, G., Panza, N., Comella, G., et al.[2022]

A variety of new agents, including taxanes, gemcitabine, and irinotecan, have shown promise in early clinical studies for treating non-small-cell lung cancer (NSCLC), indicating potential for improved treatment options.

Cisplatin remains a key component in combination therapies for NSCLC, being tested alongside these new agents, radiation, and surgery in numerous trials to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in metastatic non-small-cell lung cancer. Sandler, A.[2022]

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

In a systematic review and network meta-analysis of first-line treatments for metastatic nonsquamous non-small-cell lung cancer (NSq-NSCLC), the combination of pembrolizumab, pemetrexed, and platinum showed a statistically significant improvement in overall survival compared to various other regimens, with hazard ratios ranging from 0.42 to 0.62.

This combination therapy had a 95.6% probability of being the most effective treatment option for overall survival in patients without known targetable mutations, indicating its strong potential as a first-line treatment for this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. Frederickson, AM., Arndorfer, S., Zhang, I., et al.[2022]

The combination of carboplatin, pemetrexed, and bevacizumab showed a response rate of 52% in 27 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC), indicating its efficacy in treating this condition.

The treatment was generally well-tolerated, with no severe grade 4 or 5 toxicities reported, although some patients experienced manageable side effects like anemia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin/pemetrexed/bevacizumab in the treatment of patients with advanced non-small-cell lung cancer: a single-institution experience. Malhotra, B., Evans, T., Weiss, J., et al.[2022]

In a study of 124 patients with treatment-naïve, metastatic nonsquamous PD-L1-positive non-small cell lung cancer, the combination of atezolizumab with carboplatin and nab-paclitaxel showed significantly improved overall survival (19.9 months) and progression-free survival (8.5 months) compared to carboplatin and nab-paclitaxel alone (14.8 months and 5.1 months, respectively).

While the combination therapy had a higher incidence of manageable adverse events like neutropenia and anemia, it still demonstrated a tolerable safety profile, suggesting it could be an effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study. Xu, B., Cheng, H., Li, K., et al.[2023]

The ANTELOPE trial is a phase II study comparing the efficacy of a pemetrexed-free regimen (atezolizumab, carboplatin, and nab-paclitaxel) against a pemetrexed-based regimen (pembrolizumab, cis-/carboplatin, and pemetrexed) in treating TTF-1 negative non-small cell lung adenocarcinoma (NSCLC/ADC).

This trial aims to enroll 136 participants across 30 sites in Germany, focusing on overall survival as the primary endpoint, which will help determine the best treatment approach for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122). Frost, N., Bleckmann, A., Griesinger, F., et al.[2023]

In a randomized phase 2 trial involving 101 patients with stage IV lung adenocarcinoma, the combination of Pemetrexed and Cisplatin (Pem-Cis) showed a significantly higher one-year survival rate of 72.0% compared to 52.9% for Docetaxel and Cisplatin (Doc-Cis).

Patients receiving Pem-Cis also experienced longer progression-free survival (12.6 months) compared to those on Doc-Cis (7.5 months), indicating that Pem-Cis may be a more effective first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma. Su, SF., Li, M., Geng, YC., et al.[2020]

Less than 25% of patients with non-small cell lung cancer (NSCLC) have early-stage disease that can be surgically removed, highlighting the need for effective treatments for advanced stages.

Cisplatin-based chemotherapy, especially in combination with newer agents like gemcitabine and paclitaxel, has shown improved survival rates and response rates exceeding 35% in advanced NSCLC, indicating its efficacy in managing this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on European randomized studies in non-small cell lung cancer. Giaccone, G., Manegold, C., Rosell, R., et al.[2007]

Citations

1. alecensa.com alecensa.com/hcp/metastatic/efficacy/response-rate-cns-results.html

Results across endpoints Results across endpoints · ALECENSA was effective in delaying CNS metastases · Primary analysis · ALECENSA reduced the risk of CNS metastases vs crizotinib | IRC.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5744742/

Real-world usage and clinical outcomes of alectinib among ... The objective response rate was higher than in clinical trials (67.1% vs 51.3%, respectively) as was the disease control rate (89.9% vs 78.8%, respectively), ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8608

Real-world comparative outcomes of alectinib and ... Conclusions: In this real-world study, both alectinib and brigatinib provided favorable survival outcomes in patients with ALK-positive NSCLC.

4. alecensa.com alecensa.com/hcp/metastatic/efficacy/survival-results.html

Survival results for ALECENSA® (alectinib) PFS by IRC: In the ITT population, mPFS was 25.7 months for ALECENSA (95% CI: 19.9, NE) compared with 10.4 months with crizotinib (95% CI: 7.7, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0169500225006543

Advanced-stage ALK-positive non–small-cell lung cancer ... Among 382 patients receiving 1L alectinib overall survival (OS) rate was 88.7 % and 73.3 % at 24 and 60 months, respectively. Median progression ...

6. alecensa.com alecensa.com/hcp/metastatic/side-effects-and-safety/safety-profile.html

ALECENSA® (alectinib) safety profile See safety data from the ALK+ mNSCLC pivotal clinical trial ... Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31706099/

Pooled overall survival and safety data from the pivotal ... alectinib has robust clinical activity and a manageable safety profile in patients with advanced, ALK+ NSCLC pretreated with crizotinib.

8. onclive.com onclive.com/view/safety-data-help-affirm-adjuvant-alectinib-as-a-new-soc-in-alk-nsclc

Safety Data Help Affirm Adjuvant Alectinib as a New SOC ... Hidehito Horinouchi, MD, PhD, discusses safety data from the ALINA trial of adjuvant alectinib in ALK-positive non–small cell lung cancer.

9. gene.com gene.com/assets/frontend/downloads/media/news-features/fda-approves-new-treatment-option-for-specific-type-of-lung-cancer/0327_Alecensa-Fact-Sheet_2019-09-04.pdf

ALECENSA® (alectinib) Fact Sheet NP28673 is a Phase II global, single-arm, open-label, multicenter trial evaluating the safety and efficacy of ALECENSA (600 mg orally twice daily) in 138 people ...

10. alecensa.com alecensa.com/hcp/adjuvant/side-effects/safety-profile.html

The safety observed in the ALINA trial was consistent with ... The safety observed in the ALINA trial was generally consistent with the established ALECENSA safety profile. Most adverse reactions from the trial were mild ...