Atezolizumab + Tiragolumab + Ipatasertib for Cancer

(UmbrellaMAX Trial)

Recruiting at 62 trial locations

Overseen By Reference Study ID Number: BX44273 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Roche IMP

Must not be taking: Anti-cancer treatments

Disqualifiers: SAEs, Concurrent trials, 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: Unknown

Duration: Until disease progression or other specified criteria

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to continue treatment for cancer patients who benefited from specific medications in a previous study. The focus is on using drugs like Ipatasertib, either alone or with other treatments, to determine if they continue to control cancer. Suitable candidates are those already on these treatments who see positive effects but cannot access the medicine outside the trial. As a Phase 3 trial, this study serves as the final step before FDA approval, providing patients access to potentially groundbreaking treatments.

Do I have to stop taking my current medications for this trial?

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

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

Research has shown that the combination of atezolizumab, tiragolumab, and ipatasertib is generally safe. One study found that this drug mix caused fewer liver-related side effects compared to similar treatments. Another study showed that using tiragolumab with atezolizumab was generally easy for patients to handle, as they didn't experience severe problems. These findings suggest that the treatment is well-tolerated in humans, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they bring innovative approaches to cancer therapy. Atezolizumab, Tiragolumab, and Ipatasertib each have unique mechanisms of action that set them apart from traditional options like chemotherapy and standard immunotherapy. Atezolizumab is an immune checkpoint inhibitor targeting PD-L1, which helps the immune system recognize and attack cancer cells more effectively. Tiragolumab, also an immune checkpoint inhibitor, targets TIGIT, a novel pathway that may enhance the immune response when used with Atezolizumab. Ipatasertib is an AKT inhibitor that targets cancer cell growth pathways, potentially improving outcomes when combined with other treatments. Together, these treatments offer a multi-faceted approach to tackling cancer, potentially increasing effectiveness and broadening the range of treatable tumors.

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

Research shows that using tiragolumab with atezolizumab holds promise for treating solid cancers, such as non-small cell lung cancer. Studies have found that this combination can significantly extend the time patients live without their cancer worsening. Tiragolumab blocks a protein called TIGIT, which usually prevents immune cells from attacking cancer cells. By blocking TIGIT, tiragolumab and atezolizumab help the immune system fight cancer more effectively. However, in some cases, this combination has not improved overall survival compared to using atezolizumab alone in certain lung cancer patients. In this trial, some participants will receive the combination of tiragolumab and atezolizumab, while others will receive ipatasertib, which might further boost the treatment by targeting cancer cell growth. ^{2 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 cancer patients who were part of a previous Genentech or Roche study and are still benefiting from the treatment but can't get it outside the study. They must start this extension within 7 days after their last dose in the original study and be able to follow this new study's rules.

Inclusion Criteria

My current Roche treatment is working as determined by my doctor.

First dose of study treatment in this extension study will be received within 7 days of the treatment interruption window allowed by the parent study

Eligible for continuing Roche IMP-based therapy at the time of roll-over from the parent study, as per the parent study protocol OR eligible for continuing the comparator agent(s) in a Genentech- or Roche-sponsored study as per the parent study protocol, with no access to commercially available comparator agent

Exclusion Criteria

Meet any of the study treatment discontinuation criteria specified in the parent study at the time of enrollment in this extension study

Concurrent participation in any therapeutic clinical trial (other than the parent study)

I haven't received any cancer treatments not allowed in the main study before starting this extension study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue to receive Roche investigational medicinal product (IMP) monotherapy or in combination with other agents as per parent protocol

Until disease progression or other specified criteria

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may continue treatment with Roche IMP(s) if they do not have local access to the study treatment

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Ipatasertib

Trial Overview The trial continues treatment with Atezolizumab, Tiragolumab, Ipatasertib, or combinations thereof for participants previously receiving these drugs. It aims to provide ongoing access to these medications when they're not available commercially.

How Is the Trial Designed?

Group I: Roche IMP(s) Monotherapy Experimental Treatment 5 Interventions

Participants will continue to receive Roche IMP(s) monotherapy as per parent protocol, until disease progression, loss of clinical benefit as judged by the investigator, death, withdrawal of study consent, unacceptable toxicity, pregnancy, participants non-compliance, if local access becomes available or study termination by the Sponsor, whichever occurs first.

Group II: Roche Combined Agents Experimental Treatment 5 Interventions

Participants will continue to receive Roche IMP(s) in combination with other agent(s) as per parent protocol, until disease progression, loss of clinical benefit as judged by the investigator, death, withdrawal of study consent, unacceptable toxicity, pregnancy, participants non-compliance, if local access becomes available or study termination by the Sponsor, whichever occurs first.

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

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]

Immune checkpoint inhibitors like ipilimumab, nivolumab, and pembrolizumab have shown remarkable efficacy in treating various advanced cancers, representing a significant advancement over traditional chemotherapy.

These treatments can lead to immune-related adverse events (irAEs), which may affect any body system and can be life-threatening, highlighting the importance of prompt recognition and management by oncologists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing adverse effects of immunotherapy. Gerson, JN., Ramamurthy, C., Borghaei, H.[2018]

Tiragolumab, a TIGIT inhibitor, shows promise in treating solid cancers, particularly non-small cell lung cancer, based on results from phase I and II trials.

The combination of tiragolumab with the PD-L1 inhibitor atezolizumab has demonstrated statistically significant efficacy in multiple solid tumors, suggesting a potential new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiragolumab Impresses in Multiple Trials. [2021]

Atezolizumab combined with chemotherapy showed promising efficacy in treating advanced, treatment-naïve non-small-cell lung cancer (NSCLC), with overall response rates of 36% to 68% across different chemotherapy regimens in a study of 76 patients.

The treatment was generally well tolerated, although common severe side effects included neutropenia and anemia, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. Liu, SV., Camidge, DR., Gettinger, SN., et al.[2022]

Atezolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, can cause rare but serious immune-related adverse events (irAEs) such as acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP).

In a case study of a patient receiving atezolizumab, the development of AKI and ITP occurred one week after treatment initiation, but with appropriate management including IVIG and steroids, the patient's condition improved and was discharged for routine follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. Yılmaz, A., Mirili, C., Bilici, M., et al.[2022]

Immune checkpoint inhibitors like ipilimumab, nivolumab, pembrolizumab, and atezolizumab can lead to long-lasting tumor responses in various cancers, but they also cause immune-related adverse events (irAEs) due to the activation of the immune system.

Nivolumab, pembrolizumab, and atezolizumab generally have a lower incidence of severe toxicities compared to ipilimumab, highlighting the importance of understanding the different toxicity profiles for effective management of irAEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of Toxicities of Immune Checkpoint Inhibitors]. Horio, Y.[2017]

This phase I clinical trial is investigating the safety and efficacy of combining the anti-TIGIT monoclonal antibody tiragolumab with the PD-L1 inhibitor atezolizumab and Stereotactic Body Radiation Therapy (SBRT) in patients with metastatic non-small cell lung cancer and other cancers previously treated with immune checkpoint inhibitors.

The primary goal of the trial is to assess the safety of this combination treatment and to evaluate its effectiveness in improving 6-month progression-free survival (PFS), with the study including multiple cancer types and a focus on immune biomarker assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer. Roussot, N., Fumet, JD., Limagne, E., et al.[2023]

Atezolizumab, an immune checkpoint inhibitor, is being tested in a phase II trial for its safety and efficacy in patients with advanced non-small cell lung cancer (NSCLC) who also have chronic fibrotic interstitial pneumonia, with a focus on a 1-year survival rate among 38 participants.

This study is significant as it aims to establish a treatment option for a patient group that currently lacks standard second-line therapies, potentially improving outcomes for those with both NSCLC and interstitial pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of atezolizumab for pretreated advanced/recurrent non-small cell lung cancer with idiopathic interstitial pneumonias: rationale and design for the TORG1936/AMBITIOUS study. Ikeda, S., Kato, T., Kenmotsu, H., et al.[2022]

In a phase 1b study involving 27 patients with non-small cell lung cancer (NSCLC), the combination of atezolizumab and ipilimumab showed promising efficacy, with 26% of patients achieving confirmed responses, particularly among those who had not previously received checkpoint inhibitors.

The treatment was found to have a manageable safety profile, with no dose-limiting toxicities reported and common adverse events including dyspnea and cough, indicating that the combination therapy is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of Atezolizumab Plus Ipilimumab in Locally Advanced or Metastatic Non-Small Cell Lung Cancer: Results From a Phase 1b Trial. Wong, DJ., Bauer, TM., Gordon, MS., et al.[2022]

In the CITYSCAPE trial involving 275 patients with chemotherapy-naive, PD-L1-positive non-small-cell lung cancer, the combination of tiragolumab and atezolizumab resulted in a significantly higher objective response rate (31.3% vs. 16.2%) and improved median progression-free survival (5.4 months vs. 3.6 months) compared to placebo plus atezolizumab.

The safety profile of tiragolumab plus atezolizumab was generally similar to that of atezolizumab alone, with serious treatment-related adverse events occurring in 21% of patients in the combination group, indicating that this combination therapy is well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. Cho, BC., Abreu, DR., Hussein, M., et al.[2022]

In a phase 3 trial involving 501 patients with unresectable hepatocellular carcinoma, the combination of atezolizumab and bevacizumab significantly improved overall survival (67.2% at 12 months) and progression-free survival (6.8 months) compared to sorafenib.

The treatment with atezolizumab-bevacizumab showed a lower risk of death (hazard ratio 0.58) and similar rates of severe adverse events compared to sorafenib, indicating a favorable safety profile despite some instances of grade 3 or 4 hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. Finn, RS., Qin, S., Ikeda, M., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-4-malignancies-5-2023-19d86

Atezolizumab + Tiragolumab + Ipatasertib for Cancer The combination of tiragolumab and atezolizumab has shown effectiveness in treating solid cancers, including non-small cell lung cancer, in multiple trials.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10249258/

Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer ... The results revealed significantly prolonged progression-free survival of the tiragolumab plus atezolizumab arm in the total population (HR 0.62 ...

3. onclive.com onclive.com/view/tiragolumab-plus-atezolizumab-fails-to-meet-survival-end-points-in-previously-untreated-pd-l1-high-nsclc

Tiragolumab Plus Atezolizumab Fails to Meet Survival End ... First-line tiragolumab plus atezolizumab did not improve PFS and OS vs atezolizumab alone in PD-L1–high, unresectable or metastatic NSCLC.

4. clinicaltrials.eu clinicaltrials.eu/inn/tiragolumab/

Tiragolumab: A Promising New Immunotherapy Drug By blocking TIGIT, tiragolumab helps activate immune cells to recognize and attack cancer cells more effectively. When used in combination with atezolizumab, ...

5. ascopubs.org ascopubs.org/doi/10.1200/EDBK_432524

Non–Small Cell Lung Cancer Metastatic Without ... Interestingly, a high IC expression alone is a negative prognostic marker associated with reduced survival with atezolizumab and chemotherapy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11258083/

Phase I pharmacokinetic, safety, and preliminary efficacy ... In this study, tiragolumab plus atezolizumab was tolerable and demonstrated preliminary anti-tumor activity. There were no meaningful differences in the PK or ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38451273/

Phase I pharmacokinetic, safety, and preliminary efficacy ... Results: In this study, 20 patients received a median of five doses of tiragolumab plus atezolizumab. Median age was 57.5 years, 85.0% of ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03337698

NCT03337698 | A Study Of Multiple Immunotherapy-Based ... Participants in the Atezolizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

9. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-tiragolumab-atezolizumab-and-drug-combination-for-patients-with-urothelial-carcinoma/

Study on the Effectiveness and Safety of Tiragolumab ... This clinical trial investigates the effectiveness and safety of Tiragolumab and Atezolizumab in treating urothelial carcinoma, a cancer affecting the ...