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 (atezolizumab), in combination with Avastin (bevacizumab), paclitaxel and carboplatin, is indicated for the first-line treatment of adult patients with metastatic non-squamous non-small cell lung cancer (mNSCLC). In patients with EGFR mutant or ALK-positive mNSCLC, TECENTRIQ, in combination with bevacizumab, paclitaxel and carboplatin, is indicated only after failure of appropriate targeted therapies.

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, and whose tumours have a PD-L1 expression ≥5%

Lung Cancer

1L mNSCLC / IMpower150

Phase III multicentre, international, randomised, open-label, 3-arm trial evaluating TECENTRIQ in combination with carboplatin/paclitaxel with or without Avastin (bevacizumab) in chemotherapy-naïve patients with metastatic non-squamous mNSCLC.

Co-primary endpoints: overall survival (OS) & progression-free survival (PFS). Key secondary endpoints: overall response rate (ORR), duration of response (DoR).

A total of 1,202 patients were enrolled and were randomised (1:1:1) to receive TECENTRIQ in combination with carbo/pac with or without Avastin. Data only from the TECENTRIQ+Avastin+carbo/pac versus Avastin & carbo/pac arm are shown in the results

TECENTRIQ* combination: demonstrated survival benefit against a proven regimen in mNSCLC.1

  • Median OS was higher in TECENTRIQ* combination vs Avastin+carbo/pac arm (19.8 months vs 14.9 months; HR=0.76 (95% CI, 0.63, 0.93; P<0.006).

  • Median 12-month PFS was greater in TECENTRIQ* combination vs Avastin+carbo/pac (38% vs 20%; HR=0.59; 95% CI,0.50,0.69; P<0.0001)​

​​TECENTRIQ* is the first cancer immunotherapy combination to demonstrate clinically meaningful survival in EGFR/ALK+ and liver metastases mNSCLC patients.1,2

HR= Hazard ratio
ITT= Intention-to-treat

  • First cancer immunotherapy to show meaningful OS advantage in EGFR/ALK+ patients treated with TECENTRIQ* combination who have progressed on TKIs (not reached vs 17.5 months; HR= 0.54; 95% CI, 0.29, 1.03) and liver metastases patients (13.3 months vs 9.4 months; HR 0.52 (95% CI, 0.33, 0.82).

DURABLE RESPONSES WITH TECENTRIQ* COMBINATION THERAPY1,2

  • ORR was 56.4% (95% CI, 51.4, 61.4) with TECENTRIQ* combination vs 40.2% (95% CI, 35.3, 45.2) with Avastin+carbo/pac

  • TECENTRIQ* combination delivered a manageable and generally well-tolerated safety profile.

TECENTRIQ*= TECENTRIQ+Avastin+carboplatin/paclitaxel

2L NSCLC / 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.1,3

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

  • 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)

Bladder Cancer

Tecentriq mUC bladder cancer approval

1L mUC / IMvigor210

Phase II, 2-cohort, multicentre, international, single-arm trial in locally advanced or metastatic urothelial carcinoma (N=438)4,5

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


2L mUC / 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).

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

IC=tumour-infiltrating immune cell.

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

Safety Profile

Adverse reactions for TECENTRIQ as monotherapy

The safety of TECENTRIQ as monotherapy is based on pooled data in 3,075 patients across multiple tumour types. The most common adverse reactions (>10%) were fatigue (35.5%), decreased appetite (26%), nausea (23.7%), cough (20.7%), dyspnoea (20.7%), pyrexia (19.9%), diarrhoea (19.8%), rash (19.2%), back pain (15.3%), vomiting (15.3%), asthenia (14.8%), arthralgia (13.9%), pruritus (12.5%) and urinary tract infection (11.7%).

ARs=adverse reactions. *Includes reports of rash, rash maculopapular, erythema, rash pruritic, dermatitis acneiform, eczema, dermatitis, rash erythematous, rash macular, rash papular, skin ulcer, folliculitis, skin exfoliation, erythema multiforme, rash pustular, dermatitis bullous, acne, furuncle, palmar-plantar erythrodysaesthesia syndrome, seborrhoeic dermatitis, dermatitis allergic, drug eruption, rash generalised, erythema of eyelid, skin toxicity, toxic epidermal necrolysis, toxic skin eruption, dermatitis exfoliative, exfoliative rash, eyelid rash, fixed eruption, generalised erythema, rash papulosquamous, and rash vesicular.
 

Low incidence of immune-related ARs across monotherapy studies (N=3178)

Immune-related hypophysitis and nephritis occurred in <0.1% of patients treated with TECENTRIQ monotherapy. Immune-related myocarditis occurred in <0.1% of patients across all TECENTRIQ clinical trials. <1% of patients discontinued treatment due to an immune-related AR.

Adverse reactions for TECENTRIQ as combination therapy

The safety of TECENTRIQ given in combination with paclitaxel and carboplatin, with or without Avastin, has been evaluated in 793 patients with metastatic NSCLC. The most common adverse reactions (>20%) were peripheral neuropathy (42.6%), nausea (35.6%), anaemia (32.7%), neutropenia (32.4%), fatigue (29.8%), rash (29.8%), constipation (27.2%), decreased appetite (26.2%), diarrhoea (26.0%), thrombocytopenia (24.0%), arthralgia (23.8%).

Adverse reactions (ARs) in ≥10% of patients treated with TECENTRIQ + Avastin + carbo/pac and at a higher incidence* than in patients with Avastin + carbo/pac alone.8

*Between-arm difference of ≥5% (all grades) or ≥2% (grades 3-4).
†Three patients receiving TECENTRIQ + Avastin + carbo/pac had grade 5 febrile neutropenia.

Low incidence of immune-related ARs with TECENTRIQ +Avastin+carbo/pac (N=1,202).8

ARs=adverse reactions
‡ The incidence of hypophysitis occurred with TECENTRIQ+Avastin+carbo/pac. All other incidences occurred with TECENTRIQ monotherapy, as no clinically relevant differences were observed with the combination. Immune-related myocarditis occurred in <1.0% of patients across all TECENTRIQ clinical trials. §Bleeding events included haemoptysis, haematuria, pulmonary haemorrhage, cerebral haemorrhage, intestinal haemorrhage, large intestinal haemorrhage and cerebrovascular accident.

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. March 2019.

  2. TECENTRIQ Core Data Sheet. Version Version 13.0. Roche. February 2019.

  3. 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.

  4. 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.

  5. 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.

  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.

  8. Socinski MA, Jotte R, Cappuzzo F, et al; IMpower150 Study Group. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378:2288-2301.

Date of preparation: March 2019 l PR/ATEZ/1704/0013d(1)