Targeted Therapy + Immunotherapy for Advanced Cancer

Recruiting at 148 trial locations

Overseen By Reference Study ID Number: BO41932 https://forpatients.roche.com/

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Disqualifiers: Cardiovascular disease, Active cancer, 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: 28-day cycles

920 Participants Needed

Trial Summary

What is the purpose of this trial?

TAPISTRY is a Phase II, global, multicenter, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in rational, specified combinations in participants with unresectable, locally advanced or metastatic solid tumors determined to harbor specific oncogenic genomic alterations or who are tumor mutational burden (TMB)-high as identified by a validated next-generation sequencing (NGS) assay. Participants with solid tumors will be treated with a drug or drug regimen tailored to their NGS assay results at screening. Participants will be assigned to the appropriate cohort based on their genetic alteration(s). Treatment will be assigned on the basis of relevant oncogenotype, will have cohort-specific inclusion/exclusion criteria, and, unless otherwise specified, will continue until disease progression, loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had any anticancer treatment within 2 weeks or 5 half-lives before starting the study treatment.

What data supports the effectiveness of the drug trastuzumab emtansine (T-DM1) in treating advanced cancer?

Trastuzumab emtansine (T-DM1) has shown effectiveness in treating HER2-positive metastatic breast cancer, especially in patients who have already received other standard treatments. It combines targeted therapy with a powerful cancer-fighting agent, showing better results and fewer side effects compared to some standard treatments. ^{1 2 3 4 5}

Is trastuzumab emtansine (T-DM1) generally safe for humans?

Trastuzumab emtansine (T-DM1) has been studied in patients with HER2-positive metastatic breast cancer and has shown improved tolerability compared to standard treatments, indicating it is generally safe for humans. ^{1 3 6 7 8}

What makes this drug combination unique for advanced cancer treatment?

This drug combination is unique because it combines targeted therapies like trastuzumab emtansine, which specifically attacks cancer cells with a certain protein (HER2), with immunotherapy drugs like atezolizumab that help the immune system fight cancer more effectively. This approach aims to enhance the body's natural defenses while directly targeting cancer cells, potentially improving outcomes for patients with advanced cancer. ^{2 9 10 11 12}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

Adults and children with advanced, inoperable or metastatic solid tumors that have specific genetic changes identified by a special test. They must be physically able to participate (with varying performance scores based on age), have no other treatments available or have progressed after treatment, and not be pregnant or breastfeeding. Participants need to agree to use effective contraception.

Inclusion Criteria

For female participants of childbearing potential: Negative serum pregnancy test <= 14 days prior to initiating study treatment; agreement to remain abstinent or use single or combined contraception methods that result in a failure rate of < 1% per year for the period defined in the cohort-specific inclusion criteria; and agreement to refrain from donating eggs during the same period

I am a man willing to use contraception or remain abstinent as required.

Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), Response Assessment in Neuro-Oncology (RANO) criteria, or International Neuroblastoma Response Criteria (INRC)

Exclusion Criteria

History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study or confounds the ability to interpret data from the study

I haven't had cancer treatment in the last 2 weeks or 5 half-lives before starting this study.

Pregnant or breastfeeding, or intending to become pregnant during the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive targeted therapies or immunotherapy based on their genetic alterations in repeated cycles until disease progression or other discontinuation criteria are met

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately up to 12 years

Treatment Details

Interventions

• Alectinib
• Atezolizumab
• Belvarafenib
• Entrectinib
• Idasanutlin
• Inavolisib
• Ipatasertib
• Pralsetinib
• Trastuzumab emtansine

Trial Overview The TAPISTRY trial is testing how well different targeted therapies or immunotherapies work for patients whose tumors have certain genomic alterations or high mutation burdens. Patients receive personalized treatment based on their tumor's genetic profile, which could include drugs like Ipatasertib, Atezolizumab, etc., alone or combined.

Participant Groups

Group I: Cohort N: SETD2 LOF Tumors Experimental Treatment 1 Intervention

Participants with methyltransferase SET (Su(var) 3-9) Enhancer of zest and Trithorax) domain-containing 2 (SETD2) LOF tumors will self-administer camonsertib orally at home (except on clinic days).

Group II: Cohort M: Ataxia-telangiectasia Mutated (ATM) Loss of Function (LOF) Tumors Experimental Treatment 1 Intervention

Participants with ATM LOF tumors will self-administer camonsertib orally at home (except on clinic days).

Group III: Cohort L: KRAS G12C-positive Tumors (Excluding NSCLC and Colorectal Cancer [CRC]) Experimental Treatment 1 Intervention

Participants with kirsten rat sarcoma virus (KRAS) G12C-positive tumors will self-administer divarasib (GDC-6036) orally at home (except on clinic days).

Group IV: Cohort K: Rearranged During Transfection (RET) Fusion-positive Tumors (Excluding NSCLC) Experimental Treatment 1 Intervention

Participants with RET fusion-positive tumors will self-administer pralsetinib orally at home (except on clinic days) on a continuous daily dosing regimen at a dose of 400 mg/day (four 100-mg capsules per day) for adult and pediatric participants ≥ 12 and \< 18 years of age. A treatment cycle consists of 4 weeks (28 days). Note: Cohort K has been closed for enrollment.

Group V: Cohort J: BRAF Class III Mutant-positive Tumors Experimental Treatment 1 Intervention

Participants with BRAF class III mutant-positive tumors (adults and adolescents ≥ 40 kg) will receive 400 mg belvarafenib PO BID with adequate water (more than 200 mL). One cycle consists of 28 days. Administration of belvarafenib should occur BID on every day of each 28-day cycle. Note: Cohort J has been closed for enrollment.

Group VI: Cohort I: BRAF Class II Mutant or Fusion-positive Tumors Experimental Treatment 1 Intervention

Participants with proto-oncogene B-Raf (BRAF) class II mutant/fusion-positive tumors (adults and adolescents ≥ 40 kg) will receive 400 mg belvarafenib, PO, BID with adequate water (more than 200 milliliters \[mL\]). One cycle consists of 28 days. Administration of belvarafenib should occur BID on every day of each 28-day cycle. Note: Cohort I has been closed for enrollment.

Group VII: Cohort H: PIK3CA Multiple Mutant-positive Tumors Experimental Treatment 1 Intervention

Participants with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) multiple mutant-positive tumors will receive inavolisib (GDC-0077) QD at a starting dose of 9 mg by mouth (PO) in repeated 28-day cycles. Note: Cohort H has been closed for enrollment.

Group VIII: Cohort F: Human Epidermal Growth Factor Receptor 2 (HER2) Mutant-positive Tumors Experimental Treatment 1 Intervention

Participants with metastatic or advanced solid tumors will receive trastuzumab emtansine IV at a dose of 3.6 mg/kg every 21 days. Note: Cohort F has been closed as of protocol version 7 because enrollment and participant follow-up have been completed.

Group IX: Cohort E: Protein Kinase B (AKT) 1/2/3 Mutant-positive Tumors Experimental Treatment 1 Intervention

Participants with metastatic or advanced solid tumors will receive ipatasertib orally, QD at the starting dose of 400 mg in repeated 28-day cycles until the participant experiences disease progression, intolerable toxicity, or withdraws consent. For participants 12-17 years of age, ipatasertib will be administered at the starting dose of 200 mg for participants \< 35 kilograms (kg), 300 mg for participants ≥ 35 and \< 45 kg, 400 mg for those ≥ 45 kg orally QD in repeated 28-day cycles until the participant experiences disease progression, intolerable toxicity, or withdraws consent. Note: Cohort E has been closed for enrollment.

Group X: Cohort D: TMB-high Tumors Experimental Treatment 1 Intervention

Participants with metastatic or advanced solid tumors will receive atezolizumab intravenously (IV) at a fixed dose for participants aged ≥ 18 years, and 15 milligrams per kilogram (mg/kg) (maximum 1200 mg) for participants aged \< 18 years on Day 1 of each 21-day cycle. Note: Cohort D has been closed for enrollment.

Group XI: Cohort C: Anaplastic Lymphoma Kinase (ALK) Fusion-positive Tumors (Excluding NSCLC) Experimental Treatment 1 Intervention

Participants with metastatic or advanced solid tumors, with the exception of NSCLC, will receive alectinib at a dosage of 600 mg, orally, twice a day (BID), taken with food, in repeated 28-day cycles.

Group XII: Cohort B: Neurotrophic Tyrosine Receptor Kinase (NTRK) 1/2/3 Fusion-positive Tumors Experimental Treatment 1 Intervention

Participants with metastatic or advanced solid tumors will receive entrectinib, QD in repeated 28-day cycles at a dose of 600 mg/day for adults and pediatric participants with a BSA ≥ 1.51 m\^2. The total dose of daily entrectinib administration for pediatric participants with BSA \< 1.51 m\^2 will be lower.

Group XIII: Cohort A: ROS Proto-oncogene 1 (ROS1) Fusion-positive Tumors (Excluding NSCLC) Experimental Treatment 1 Intervention

Participants with metastatic or advanced solid tumors, with the exception of non-small cell lung cancer (NSCLC), will receive entrectinib once daily (QD) in repeated 28-day cycles at a dose of 600 milligram per day (mg/day) for adults and pediatric participants with a body surface area (BSA) ≥ 1.51 square meter (m\^2). The total dose of daily entrectinib administration for pediatric participants with BSA \< 1.51 m\^2 will be lower.

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

Findings from Research

In a phase Ib trial involving 20 patients with HER2-positive metastatic breast cancer, the combination of trastuzumab emtansine (T-DM1) and pembrolizumab was found to be safe and tolerable, with no dose-limiting toxicities reported.

The treatment resulted in an objective response rate of 20% and a median progression-free survival of 9.6 months, indicating potential efficacy, although immune biomarkers did not correlate with treatment response in this small cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. Waks, AG., Keenan, TE., Li, T., et al.[2022]

In a study of 110 patients with HER2-positive metastatic breast cancer who had previously received multiple treatments, the antibody-drug conjugate trastuzumab emtansine (T-DM1) showed an overall response rate of 34.5% and a clinical benefit rate of 48.2%, indicating its effectiveness as a treatment option.

T-DM1 was well tolerated, with most side effects being mild (grades 1 to 2), and the most common severe side effects included thrombocytopenia and fatigue, suggesting a favorable safety profile for patients who have exhausted other HER2-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. Krop, IE., LoRusso, P., Miller, KD., et al.[2022]

Trastuzumab emtansine (T-DM1) has shown a favorable safety profile in 884 patients with HER2-positive metastatic breast cancer, with most adverse events being manageable and asymptomatic, such as fatigue and nausea.

The treatment demonstrated superior efficacy compared to standard therapies in previous studies, making T-DM1 a promising option for further exploration in other breast cancer settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. Diéras, V., Harbeck, N., Budd, GT., et al.[2019]

In a phase 3 trial involving 1486 patients with HER2-positive early breast cancer, adjuvant treatment with trastuzumab emtansine (T-DM1) significantly reduced the risk of invasive disease or death by 50% compared to trastuzumab alone, with 12.2% of patients in the T-DM1 group experiencing these events versus 22.2% in the trastuzumab group.

The estimated 3-year invasive disease-free survival rate was 88.3% for the T-DM1 group compared to 77.0% for the trastuzumab group, indicating that T-DM1 is more effective in preventing recurrence after neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. von Minckwitz, G., Huang, CS., Mano, MS., et al.[2022]

In a study involving 27 patients with HER2-positive metastatic breast cancer who had progressed on previous therapies, the combination of ado-trastuzumab emtansine (T-DM1) and neratinib showed promising efficacy, with 63% of evaluable patients achieving an objective response.

The recommended phase II dose for this combination was established as T-DM1 at 3.6 mg/kg and neratinib at 160 mg/d, with manageable safety profiles, although some patients experienced grade 3 toxicities like diarrhea and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of T-DM1 Plus Neratinib in Patients With Metastatic HER2-Positive Breast Cancer: NSABP Foundation Trial FB-10. Abraham, J., Montero, AJ., Jankowitz, RC., et al.[2020]

In a phase IIa study involving 64 patients with HER2-positive metastatic breast cancer, the combination of trastuzumab emtansine (T-DM1) and pertuzumab showed an overall objective response rate (ORR) of 41%, with a higher ORR of 57% in first-line patients, indicating promising efficacy for this treatment.

The combination therapy was generally safe, with common side effects including fatigue (61%) and nausea (50%), and no unexpected toxicities were reported, suggesting that this treatment can be administered at full doses without significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer. Miller, KD., Diéras, V., Harbeck, N., et al.[2022]

In a study of 232 Japanese patients with HER2-positive advanced breast cancer, trastuzumab emtansine (T-DM1) was found to be well tolerated, with 98.3% of patients experiencing adverse events but only 2.2% discontinuing treatment due to these events.

The most common serious adverse effects included thrombocytopenia in 29.7% of patients and hepatotoxicity in 11.2%, but no new safety concerns were identified, indicating that T-DM1 is a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer. Watanabe, J., Ito, Y., Saeki, T., et al.[2022]

Ado-trastuzumab emtansine (T-DM1) was approved in the U.S. for treating HER2 positive metastatic breast cancer based on the EMILIA phase III trial, which showed it was more effective than the standard treatment of lapatinib plus capecitabine.

Ongoing and planned trials are exploring T-DM1's use in various stages of breast cancer, and the review discusses its toxicity management and potential resistance mechanisms, highlighting its importance in current cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. Peddi, PF., Hurvitz, SA.[2022]

The ASTEFANIA trial is designed to assess the effectiveness of combining atezolizumab, an immunotherapy, with ado-trastuzumab emtansine in treating high-risk, HER2-positive early breast cancer patients who have residual disease after initial HER2-targeted therapy.

This study will involve 1700 participants across 32 countries, focusing on invasive disease-free survival as the primary outcome, while also evaluating safety and pharmacokinetics, highlighting the potential for enhanced treatment strategies in early-stage breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASTEFANIA: adjuvant ado-trastuzumab emtansine and atezolizumab for high-risk, HER2-positive breast cancer. Hurvitz, SA., Bachelot, T., Bianchini, G., et al.[2022]

The combination of atezolizumab with trastuzumab emtansine did not significantly improve progression-free survival in patients with HER2-positive metastatic breast cancer compared to trastuzumab emtansine alone, with a median survival of 8.2 months versus 6.8 months, indicating no clinically meaningful benefit.

Patients receiving atezolizumab experienced a higher frequency of adverse events, including serious complications, suggesting that this combination therapy may pose additional risks without clear advantages in efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Emens, LA., Esteva, FJ., Beresford, M., et al.[2020]

In the phase III KAITLIN study involving 1846 adults with high-risk HER2-positive early breast cancer, replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1) did not significantly improve invasive disease-free survival compared to the standard treatment of trastuzumab plus pertuzumab with chemotherapy.

While both treatment regimens showed favorable outcomes, the completion rate for the T-DM1 group was lower (65.0%) due to more laboratory abnormalities, indicating potential safety concerns despite similar rates of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. Krop, IE., Im, SA., Barrios, C., et al.[2023]

Atezolizumab, when combined with other therapies like trastuzumab and docetaxel, showed promising safety and efficacy in treating patients with HER2-positive metastatic breast cancer, with objective responses observed in 6 out of 6 patients in one cohort.

In early breast cancer patients, the combination of atezolizumab with trastuzumab or T-DM1 increased PD-L1 levels and CD8+ T-cell infiltration, suggesting that this treatment may enhance the immune response, although it did not promote T-cell receptor clonal expansion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Anti-HER2 Treatments Combined With Atezolizumab on the Tumor Immune Microenvironment in Early or Metastatic Breast Cancer: Results From a Phase Ib Study. Hamilton, EP., Kaklamani, V., Falkson, C., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of T-DM1 Plus Neratinib in Patients With Metastatic HER2-Positive Breast Cancer: NSABP Foundation Trial FB-10. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. [2022]

9. England pubmed.ncbi.nlm.nih.gov

ASTEFANIA: adjuvant ado-trastuzumab emtansine and atezolizumab for high-risk, HER2-positive breast cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Impact of Anti-HER2 Treatments Combined With Atezolizumab on the Tumor Immune Microenvironment in Early or Metastatic Breast Cancer: Results From a Phase Ib Study. [2022]