What is TECENTRIQ®?

Programmed death-ligand 1 (PD-L1) may be expressed on tumour cells and/or tumour-infiltrating immune cells, and can contribute to the inhibition of the antitumour immune response in the tumour microenvironment. Binding
of PD-L1 to the PD-1 and B7.1 receptors found on T-cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production.

TECENTRIQ is an Fc-engineered, humanised immunoglobulin G1 (IgG1) monoclonal antibody that directly binds to PD-L1 and provides a dual blockade of the PD-1 and B7.1 receptors, releasing PD-L1/PD-1 mediated inhibition of the immune response, including reactivating the antitumour immune response without inducing antibody-dependent cellular cytotoxicity.

TECENTRIQ spares the PD-L2/PD-1 interaction allowing PD-L2/PD-1 mediated inhibitory signals to persist.1

 

Indications

 

TECENTRIQ as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. Patients with EGFR activating mutations or ALK-positive tumour mutations should also have received targeted therapy before receiving TECENTRIQ.

TECENTRIQ as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) after prior platinum-containing chemotherapy or who are considered cisplatin ineligible.

 

 

Lung Cancer

OAK

Phase III, multicentre, international, randomised, open-label trial evaluating TECENTRIQ against docetaxel in previously treated advanced NSCLC, regardless of PD-L1 expression.

A total of 1225 patients were enrolled, with the primary analysis population consisting of the first 850 randomised patients.1,2

HR=0.73 (95% CI, 0.62, 0.87); P=0.0003
  • 55% of patients were alive at 1 year with TECENTRIQ vs 41% with docetaxel (median follow-up time was 21 months)

  • An improvement in median OS was observed with TECENTRIQ vs docetaxel in both non-squamous (15.6 vs 11.2 months; HR=0.73; 95% CI, 0.60, 0.89) and squamous (8.9 vs 7.7 months; HR=0.73; 95% CI, 0.54, 0.98) NSCLC

  • Improved survival was observed with TECENTRIQ at all levels of PD-L1 expression, including for patients with little or no expression (TC and IC <1%: 12.6 vs 8.9 months; HR=0.75)

IC=tumour-infiltrating immune cell; TC=tumour cell.

Bladder Cancer

Tecentriq mUC bladder cancer approval

IMvigor210

Phase II, 2-cohort, multicentre, international, single-arm trial in locally advanced or metastatic urothelial carcinoma (N=438)3,4

First-line patients who are ineligible for platinum-containing regimen (IMvigor210 cohort 1)

TECENTRIQ®: DURABLE RESPONSE IN FIRST-LINE, CISPLATIN-INELIGIBLE PATIENTS

IMvigor211

IMvigor211, patients previously treated with a platinum-containing regimen

Open-label, multicentre, international, randomised study evaluating TECENTRIQ vs chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who progressed during or following a platinum-containing regimen (N=931).1

Primary endpoint: overall survival (OS). Key secondary endpoints: objective response rate (ORR), progression-free survival (PFS) and duration of response (DOR).

The study used a hierarchical testing procedure that required the primary endpoint to be met in the IC2/3 population to claim a positive study outcome.

In IMvigor211 the primary pre-specified OS IC2/3 endpoint was not met.1

  • OS hazard ratio (HR) of 0.87 (95% CI, 0.63, 1.21; P=0.41)

       

       Durable responses demonstrated in the ITT population (median follow-up: 17 months)1,6,7

       

A 1-year OS of 39% in the ITT population of IMvigor211 was consistent with efficacy results seen in previously reported studies, including a 1-year OS of 37% in Cohort 2 of IMvigor210.

TECENTRIQ showed a favourable safety profile vs chemotherapy.

IMvigor211 data were generally consistent with prior TECENTRIQ studies in patients with locally advanced or metastatic urothelial carcinoma.1

IC=tumour-infiltrating immune cell.

Safety Profile

The safety of TECENTRIQ is based on pooled data in 2,160 patients with metastatic UC and NSCLC. The most common adverse reactions were fatigue (35.4%), decreased appetite (25.5%), nausea (22.9%), dyspnoea (21.8%), diarrhoea (18.6%), rash (18.6%), pyrexia (18.3%), vomiting (15.0%), arthralgia (14.2%), asthenia (13.8%) and pruritus (11.3%).1

Low incidence of ≥grade 3 treatment-related AEs across UC and NSCLC studies (N=2160)5

AEs=adverse events; NSCLC=non-small cell lung cancer; UC=urothelial carcinoma.
* Includes reports of rash maculopapular, erythema, rash pruritic, dermatitis acneiform, eczema, rash papular, rash macular, dermatitis, rash erythematous, acne, skin exfoliation, skin ulcer, seborrhoeic dermatitis, erythema multiforme, dermatitis bullous, rash generalised, skin toxicity, exfoliative rash, dermatitis allergic, drug eruption, dermatitis exfoliative, palmar-plantar erythrodysaesthesia syndrome, rash papulosquamous, toxic skin eruption, erythema of eyelid, eyelid rash, folliculitis, furuncle, and rash.

 

Low incidence of immune-related AEs across UC and NSCLC studies (N=2160)1

Additional Resources

In cancer immunotherapy research, science is changing the score. Starting with the PD-L1 pathway, Roche is taking a dynamic approach to research by exploring how to modulate the antitumour immune response.

For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever to bring personalised immunotherapy to people with cancer.

References

  1. TECENTRIQ Summary of Product Characteristics. Roche. September 2017.

  2. Rittmeyer A, Barlesi F, Waterkamp D, et al; OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389:255-265.

  3. Balar AV, Galsky MD, Rosenberg JE, et al; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. Doi: 10.1016/S0140-6736(16)32455-2.

  4. Loriot Y, Rosenberg JE, Powles T, et al. Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): updated OS, safety and biomarkers from the phase III IMvigor210 study. Poster presented at: ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Poster #738P.

  5. TECENTRIQ Core Data Sheet. Version 2.0. Roche. September 2017.

  6. Powles T, Durán I, van der Heijden MS, et al; IMvigor211 Study Group. Atezolizumab vs. chemotherapy for platinum-treated advanced urothelial carcinoma.

  7. Powles T, Loriot Y, Durán I, et al. IMvigor211: a phase III randomized study examining atezolizumab vs. chemotherapy for platinum-treated advanced urothelial carcinoma. Presented at: 2nd Special Conference EACR AACR SIC; June 24-27, 2017; Florence, Italy.

Date of preparation: October 2017 l PR/ATEZ/1704/0013d