Atezolizumab + Tiragolumab for Cancer

Overseen By Ryan Huey, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Immunostimulatory agents

Disqualifiers: Autoimmune disease, Cardiac disease, Infections, 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: 12 months

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment involving two immunotherapy drugs, atezolizumab and tiragolumab, to determine if they can control cancers of unknown origin. The study examines both the safety and effectiveness of this drug combination. It targets individuals whose cancer has not responded to standard chemotherapy or who cannot undergo it, and who have measurable cancer on medical scans. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients taking certain prohibited medications are not eligible, and those on stable anticoagulant regimens are allowed. It's best to discuss your specific medications with the trial team.

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

Research has shown that patients generally tolerate the combination of atezolizumab and tiragolumab well. Studies involving these treatments found no new safety issues, indicating safety for the participants. Another study confirmed that patients managed the treatment without serious problems.

Although this combination did not improve certain cancer outcomes compared to other treatments, the absence of unexpected safety concerns remains a key point. This is encouraging for prospective trial participants, as the treatment has been tested for safety in humans and proven manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Atezolizumab and Tiragolumab because they offer a novel approach to cancer treatment. Unlike traditional therapies that target cancer cells directly, Atezolizumab is an immune checkpoint inhibitor that unleashes the immune system to attack cancer. Tiragolumab further enhances this effect by targeting a different checkpoint pathway, potentially boosting the immune response even more. This dual-action approach could lead to better outcomes and fewer side effects compared to standard treatments.

What evidence suggests that the combination of atezolizumab and tiragolumab could be effective for cancers of unknown primary?

Research has shown that the combination of atezolizumab and tiragolumab, which participants in this trial will receive, may help treat certain cancers. In one study, nearly half of the patients experienced a significant reduction in their cancer. Another study suggested that patients might live longer, although it did not provide specific details. However, some studies found no additional benefit compared to other treatments for different types of cancer. Overall, while there are hopeful signs, the effectiveness of this treatment can depend on the type of cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Ryan Huey, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with cancer of unknown primary origin. Participants should meet specific health criteria not detailed here.

Inclusion Criteria

Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening.

I cannot tolerate or did not respond to at least one chemotherapy treatment.

My organs and bone marrow are working well.

Exclusion Criteria

I have received specific treatments.

I have cancer pain that isn't managed well.

I have recently taken antibiotics by mouth or IV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Atezolizumab and Tiragolumab to assess anti-tumor activity

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Tiragolumab

Trial Overview The study tests the effectiveness and safety of combining two immune checkpoint inhibitors, Atezolizumab and Tiragolumab, in treating cancers without a known primary source.

How Is the Trial Designed?

Group I: Treatment with Atezolizumab + Tiragolumab Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Strategic Alliance

Collaborator

Trials

2

Recruited

90+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In the phase III IMagyn050 trial involving patients with newly diagnosed ovarian cancer, the addition of atezolizumab to standard chemotherapy did not improve progression-free survival (PFS) in patients with BRCA1/2 mutations or homologous recombination deficiency (HRD).

Despite the presence of BRCA1/2 mutations or HRD, most ovarian tumors exhibited low tumor mutation burden (TMB), indicating that genomic instability does not predict enhanced sensitivity to immune checkpoint inhibitors like atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. Landen, CN., Molinero, L., Hamidi, H., et al.[2023]

In the phase III SKYSCRAPER-02 study involving 490 patients with untreated extensive-stage small-cell lung cancer, the addition of tiragolumab to atezolizumab and chemotherapy did not significantly improve progression-free survival (PFS) or overall survival (OS).

The combination treatment was well tolerated, with similar rates of immune-mediated adverse events between the tiragolumab and control groups, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. Rudin, CM., Liu, SV., Soo, RA., et al.[2023]

Atezolizumab treatment in 615 patients with previously treated advanced non-small cell lung cancer showed a median overall survival of 11.1 months and a median progression-free survival of 2.7 months, indicating its efficacy in this population.

The safety profile was manageable, with treatment-related serious adverse events occurring in 7.8% of patients and immune-related adverse events in 8.3%, confirming that atezolizumab can be safely administered even to patients with severe renal impairment and other challenging conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., et al.[2021]

Atezolizumab therapy significantly improves overall survival (median OS of 11.2 months) in patients with previously treated advanced non-small cell lung cancer (NSCLC), demonstrating its efficacy in a diverse patient population.

The treatment has a manageable safety profile, with serious adverse events occurring in only 8.0% of patients and no new safety signals identified, indicating it is a viable option for patients often excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., 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]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

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]

In a real-world study of 1002 patients with previously treated non-small cell lung cancer (NSCLC), atezolizumab showed an 18-month overall survival rate of 41.1%, confirming its effectiveness outside of clinical trial settings.

The safety profile was acceptable, with an overall adverse event rate of 43.9% and immune-related adverse events at 19.0%, but caution is advised for patients with poorer performance status (ECOG ≥ 2), as they had a significantly lower survival rate of 14.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Atezolizumab Monotherapy in Previously Treated Japanese Patients With Unresectable Advanced or Recurrent NSCLC: A Multicenter, Prospective, Observational Study (J-TAIL). Miura, S., Nishio, M., Akamatsu, H., et al.[2023]

Atezolizumab significantly improves overall survival (OS) and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, based on a meta-analysis of 7 randomized clinical trials involving 4,859 patients.

The effectiveness of atezolizumab varies based on clinical and molecular features, with better outcomes observed in younger patients, those with wild-type EGFR, and active or previous smokers, highlighting the importance of personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis. Liu, W., Huo, G., Chen, P.[2022]

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]

Citations

1. targetedonc.com targetedonc.com/view/tiragolumab-plus-atezolizumab-fails-to-improve-outcomes-as-consolidation-in-nsclc

Tiragolumab Plus Atezolizumab Fails to Improve ... Tiragolumab plus atezolizumab did not improve progression-free survival compared to durvalumab in stage III NSCLC patients post-cCRT. Median ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01363

SKYSCRAPER-02: Tiragolumab in Combination With ... Tiragolumab did not provide additional benefit over atezolizumab and CE in untreated ES-SCLC. The combination was well tolerated with no new safety signals.

3. lungcancerstoday.com lungcancerstoday.com/post/final-survival-results-from-phase-3-skyscraper-01-study-presented-at-aacr-2025

Phase 3 SKYSCRAPER-01 Study: Final PFS, OS Analyses ... Dr. Peters and colleagues explained that the combination of tiragolumab plus atezolizumab “has shown encouraging survival outcomes” in patients ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35576957/

Tiragolumab plus atezolizumab versus placebo ... Median progression-free survival was 5·4 months (95% CI 4·2-not estimable) in the tiragolumab plus atezolizumab group versus 3·6 months (2·7-4·4) ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925004708

Phase II trial of neoadjuvant atezolizumab and tiragolumab ... Atezolizumab/tiragolumab led to a 47.7 % major pathologic response (MPR) rate. •. This doublet had a low rate of treatment-related Grade 3 + ...

6. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00679-X/fulltext

Tiragolumab in combination with atezolizumab and ... PD-L1 and VEGF blockade with atezolizumab plus bevacizumab has been shown to improve survival in unresectable hepatocellular carcinoma.

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/NCT02794571

Study Details | NCT02794571 | Safety and ... This first-in-human open-label, multicenter, dose-escalation and expansion study is designed to evaluate the safety, tolerability, and PK of tiragolumab ...