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34596011000001107

Refrigerated Storage

TecentriqRoche Products Ltd

Roche Products Ltd
Tecentriq
Concentrate for solution for infusion, 840mg and 1200mg

Contact Roche Products Ltd in all cases where a deviation from the recommended storage conditions has occurred. Refer to the electronic medicines compendium (eMC) at https://www.medicines.org.uk for company contact details.

12 October 2022
London MI Service

New Medicines

TecentriqHepatocellular carcinoma (HCC) - first-line in combination with bevacizumab

Information

Tecentriq
Licence extension / variation
Roche
Roche

Development and Regulatory status

Launched
Launched
Launched
November 2020
Nov 20Approved in the EU [14]
Sep 20The CHMP has recommended approval of atezolizumab in combination with bevacizumab for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma who have not received prior systemic therapy [13].
Jun 20Granted EAMS status in UK [12].
May 20Approved in US. This was based on data from the Phase III IMbrave 150 trial. [11]
Jan 20Filed in EU [9].
Jan 20A submission of an sBLA has been made to the U.S. FDA for atezolizumab combined with bevacizumab for the treatment of people with unresectable hepatocellular carcinoma [8].
Oct 19Filings now 2020 [6].
Jan 19Filings in US & EU planned for 2019 [4].

Category

Immunotherapy, interferes with a protein called PD-L1 (Programmed Death-Ligand 1).
The age-standardised incidence rate for liver cancer in the UK in 2008 was 4.3 per 100,000 population. HCC is the most common type of primary liver cancer [1].
Hepatocellular carcinoma (HCC) - first-line in combination with bevacizumab
Intravenous

Further information

Yes

Trial or other data

May 20PIII IMbrave150 is published; the RCT (n=336) found atezolizumab combined with bevacizumab resulted in better overall (67.2% vs. 54.6% at 12 months; HR for death 0.58; 95% CI, 0.42-0.79; p<0.001) and progression-free (6.8 vs. 4.3 months; HR 0.59; 95% CI, 0.47 to 0.76; p<0.001) survival outcomes than sorafenib [10].
Nov 19PIII trial Imbrave150 found atezollizumab in combination with Avastin reduced the risk of death (OS) by 42% (hazard ratio [HR]=0.58; 95% CI: 0.42-0.79; p=0.0006) and reduced the risk of disease worsening or death (PFS) by 41% (HR=0.59; 95% CI: 0.47-0.76; p<0.0001), compared with sorafenib [7].
Oct 19PIII Imbrave150 study show combination beat SOC at stalling cancer progression and helped them live longer [5].
Jan 19Recruitment completes in PIII IMbrave150 study [4].
Jan 18First patient enrolled in PIII IMbrave150 study comparing atezolizumab plus bevacizumab with sorafenib in 480 patients in countries including the US & EU (plus UK) (NCT03434379). Primary outcomes are overall survival and objective response rate; collection of these data is due to complete May 21 [2,3].

Evidence based evaluations

Tecentriq Non-squamous non-small cell lung cancer (NSCLC) - first-line monotherapy in PD-L1 selected patients

Information

Tecentriq
Licence extension / variation
Roche
Roche

Development and Regulatory status

Launched
Launched
Launched
May 2021
May 21Licence extension approved in EU [10].
May 21Licence extension approved in UK for first-line treatment of adults with metastatic NSCLC whose tumours have a PD-L1 expression ≥ 50% tumour cells or ≥ 10% tumour-infiltrating immune cells and who do not have EGFR mutant or ALK-positive NSCLC [9].
Mar 21Recommended for EU approval by CHMP - the additional indication is "as monotherapy ... for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have a PD-L1 expression ≥ 50% tumour cells (TC) or ≥ 10% tumour-infiltrating immune cells (IC) and who do not have EGFR mutant or ALK-positive NSCLC (see section 5.1)" [20].
Jun 20Approved in US for 1st-line treatment for metastatic NSCLC with high PD-L1 expression. An accompanying FDA-approved diagnostic test is used to determine PD-L1 status [6].
May 20Approved in US [5].
Nov 19Filed in EU & US for first-line monotherapy for advanced non-squamous and squamous (NSCLC) without EGFR or ALK mutations with high PD-L1 expression [4].
Oct 19Filing for monotherapy of PD-L1 selected patients (using data from IMpower110) planned for 2020 [1].

Category

Immunotherapy, interfers with with a protein called PD-L1 (Programmed Death-Ligand 1).
UK incidence of advanced NSCLC is 40 per 100,000 people. 42% of NSCLC are squamous [3].
Non-squamous non-small cell lung cancer (NSCLC) - first-line monotherapy in PD-L1 selected patients
Intravenous

Further information

Yes

Trial or other data

Oct 20PIII IMpower110 RCT (n=572) found that atezolizumab resulted in longer overall survival than platinum-based chemotherapy in subgroup of patients with EGFR and ALK wild-type tumours with highest expression of PD-L1 (20.2 vs. 13.1 months; HR death, 0.59; p=0.01) [7].
Oct 19Roche announce PIII IMpower 110 (NCT02409342) study (n=555) met primary endpoint in interim analysis, demonstrating statistically significant OS benefit in people with high PD-L1 expression (TC3/IC3-WT) vs. chemotherapy alone [2].
Sep 15PIII IMpower 110 study begins recruitment of 570 PD-L1-selected pts with non-squamous NSCLC (and squamous) and compares atezolizumab monotherapy with carboplatin/cisplatin + pemetrexed [1].

Evidence based evaluations

SMC

TecentriqSquamous non-small cell lung cancer (NSCLC) - first-line monotherapy in PD-L1 selected patients

Information

Tecentriq
Licence extension / variation
Roche
Roche

Development and Regulatory status

Launched
Launched
Launched
May 2021
Mar 21Recommended for EU approval by CHMP - the additional indication is "as monotherapy ... for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have a PD-L1 expression ≥ 50% tumour cells (TC) or ≥ 10% tumour-infiltrating immune cells (IC) and who do not have EGFR mutant or ALK-positive NSCLC (see section 5.1)" [8].
May 20Approved in US for 1st-line treatment for metastatic NSCLC with high PD-L1 expression. An accompanying FDA-approved diagnostic test is used to determine PD-L1 status.[18]
Feb 20FDA accepts sBLA for atezolizumab as first-line monotherapy for advanced non-squamous and squamous (NSCLC) without EGFR or ALK mutations with high PD-L1 expression, for priority review [16].
Nov 19Filed in EU for first-line monotherapy for advanced non-squamous and squamous (NSCLC) without EGFR or ALK mutations with high PD-L1 expression [17].
Oct 19PIII development of atezolizumab in combination with nab-paclitaxel for first-line treatment of squamous NSCLC discontinued and no plans for filing. Filing for monotherapy of PD-L1 selected patients (using data from IMpower110) planned for 2020 [15].
Jan 19EU & US filings planned for 2019 [10].
Oct 18Filings yet to have been made [9].
Jul 16Filings now planned for 2018 [5].
Apr 15EU & US filings predicted 2018 or later [1].

Category

Immunotherapy, interfers with with a protein called PD-L1 (Programmed Death-Ligand 1).
UK incidence of advanced NSCLC is 40 per 100,000 people. 42% of NSCLC are squamous [3].
Squamous non-small cell lung cancer (NSCLC) - first-line monotherapy in PD-L1 selected patients
Intravenous

Further information

Yes

Trial or other data

Oct 20PIII IMpower110 RCT (n=572) found that atezolizumab resulted in longer overall survival than platinum-based chemotherapy in subgroup of patients with EGFR and ALK wild-type tumours with highest expression of PD-L1 (20.2 vs. 13.1 months; HR death, 0.59; p=0.01) [19].
Sep 20Updated results of PIII IMpower131 study reported at the World Conference of Lung Cancer. Median OS was 14.2 months in arm B (atezolizumab plus chemotherapy; n=343) vs 13.5 months in arm C (chemotherapy alone; n=340), not crossing the boundary for statistical significance (HR=0.88; 95% CI, 0.73-1.05; p=0.16). In the PD-L1–high tumour expression subgroup, median OS was 23.4 vs 10.2 months, respectively (HR=0.48; 95% CI, 0.29-0.81). No new safety signals were observed in this study, but the incidence of grade 3/4 treatment-related adverse events was higher for patients who received atezolizumab vs those who did not (68% vs 57.5%) [12-14].
Sep 19Roche announce PIII IMpower 110 (NCT02409342) study (n=555) met primary endpoint in interim analysis, demonstrating statistically significant OS benefit in people with high PD-L1 expression (TC3/IC3-WT) vs. chemotherapy alone [11].
Jan 19Interim OS data has been presented at ESMO 2018 [10].
Jun 18Roche announce further data from PIII IMpower131 study (n=1,021). At 12 months, median PFS in patients on atezolizumab monotherapy was 6.3 months vs 5.6 months in the chemotherapy group [8].
Mar 18Phase III clinical trial, IMpower131, of Tecentriq (atezolizumab) with carboplatin and Abraxane met its co-primary endpoint of PFS in squamous NSCLC. Although a statistically significant OS benefit wasn’t seen, the study will continue.[7]
Mar 17Recruitment complete in the PIII IMpower131 study involving 1,025 patients with squamous NSCLC. Patients have been randomised to first-line treatment in one of the 3 arms: Arm A atezolizumab plus paclitaxel + carboplatin; Arm B atezolizumab plus nab-paclitaxel + carboplatin; Arm C nab-paclitaxel + carboplatin. PFS & OS will be assessed [6].
Jul 16PIII IMpower 110 (NCT02409342) study (n=400) is currently recruiting PDL1-selected pts with squamous or non-squamous NSCLC from sites globally (including the UK). Primary outcome data collection is expected to complete Apr 2018. PIII IMpower 111 is to be consolidated into IMpower 110. IMpower 111 began in Q2 15 and is recruiting 400 PDL1-selected patients with squamous NSCLC and comparing atezolizumab monotherapy with gemcitabine plus cisplatin or carboplatin [3].
Dec 15companion diagnostic test also in development and will be required to identify suitable patients [4].
Jun 15PIII IMpower 111 (NCT02409355) study (n=400) is designed to evaluate and compare safety and efficacy of atezolizumab (MPDL3280A) compared with treatment with gemcitabine + cisplatin or carboplatin in patients with chemotherapy-naive, Stage IV squamous NSCLC. Study sites include the US & EU (inc. UK). Collection of PFS primary outcome data should complete Jul 19 [2].
Jun 15Roche announce patient enrolment begins in two PIII studies. In one, 1,200 pts will be recruited to assess the effects of RG7446 with nab-paclitaxel or paclitaxel and carboplatin vs. chemotherapy alone on progression-free survival. The second study will recruit 400 PD-L1-selected pts and compare RG7446 monotherapy vs. chemotherapy (gemcitabine + carboplatin/cisplatin) [1].

Evidence based evaluations

Tecentriq Triple negative breast cancer - first-line with Abraxane

Information

Tecentriq
Licence extension / variation
Roche
Roche

Development and Regulatory status

Launched
Filing withdrawn
Phase III Clinical Trials
September 2021
Sep 21MHRA approves a licence extension for use in combination with nab-paclitaxel for the treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer whose tumours have PD-L1 expression ≥1% and who have not received prior chemotherapy for metastatic disease [9].
Jul 21Roche withdraws its EU filing because it considered data from the main study did not allow the CHMP to conclude that the benefit-risk balance was positive. The CHMP had asked Roche to answer questions about the application, but after assessing the responses, there were still some unresolved issues and its provisional opinion was that use of Tecentriq could not be extended. CHMP considered the effect of Tecentriq in the main study was not sufficient to establish that it worked well enough [8].
Dec 20Filed in EU [7].
Apr 19Filings now 2020 [5].
Oct 17Filings now planned for 2019 [3].
Jul 17EU & US filings will not be until at least 2020 [1].

Category

Immunotherapy, interferes with a protein called PD-L1 (Programmed Death-Ligand 1).
15% of patients with breast cancer have triple negative disease.
Triple negative breast cancer - first-line with Abraxane
Intravenous

Further information

Yes

Trial or other data

Jun 20Topline data from the PIII IMpassion031 study (NCT03197935) showed that atezolizumab in combination with albumin-bound paclitaxel followed by chemotherapy was statistically significantly superior to placebo followed by chemotherapy. The primary endpoint (improving pathological complete response [pCR]) was met at 21 weeks of treatment. There was also less evidence of tumour tissue detectable at time of surgery in the treatment arm. Results were independent of PD-L1 expression [6].
Mar 19IDMC recommends expanding PIII IMpassion031 study to recruit 120 more pts (all comers and PDL1-positive) [5].
Jun 18Recruitment complete in PIII IMpassion031 [4].
Aug 17IMpassion031 study (NCT03197935) is recruiting in the US, Australia, Belgium, Brazil, Canada, Germany, Japan, South Korea, Taiwan & the UK. Collection of primary outcome data should complete Mar 19 [2].
Jul 17First patient enrolled in PIII IMpassion031 study. 204 patients will be randomised to atezolizumab or placebo, both with Abraxane (nab-paclitaxel). Primary endpoint is pathologic complete response [1].

Evidence based evaluations

TecentriqNon-small cell lung cancer (NSCLC) - early stage adjuvant therapy

Information

Tecentriq
Licence extension / variation
Roche
Roche

Development and Regulatory status

Launched
Launched
Launched
January 2022
Jun 22Approved in EU as an adjuvant treatment, following complete resection and platinum-based chemotherapy, for adults with non-small cell lung cancer (NSCLC) with a high risk of recurrence whose tumours express PD-L1≥50% and who do not have EGFR mutant or ALK-positive NSCLC [16].
Apr 22Recommended for EU approval by CHMP – the extension to the existing indication is for use as monotherapy “as adjuvant treatment following complete resection and platinum-based chemotherapy for adult patients with NSCLC with a high risk of recurrence whose tumours have PD-L1 expression on ≥ 50% of tumour cells (TC) and who do not have EGFR mutant or ALK‑positive NSCLC” [16].
Jan 22License extension approved by MHRA. Additional indication is “Tecentriq as monotherapy is indicated as adjuvant treatment following complete resection for adult patients with Stage II to IIIA non-small cell lung cancer (NSCLC) whose tumours have PD-L1 expression on ≥ 50% of tumour cells and whose disease has not progressed following platinum-based adjuvant chemotherapy” [15].
Oct 21Approved by FDA as adjuvant treatment following surgery and platinum-based chemotherapy for adults with Stage II-IIIA non-small cell lung cancer (NSCLC) whose tumors express PD-L1≥1%, as determined by an FDA-approved test [14].
Jun 21Filed in the EU and US [13].
Apr 21Filings will now be in 2021 [12].
Oct 20Filings for adjuvant treatment of NSCLC still planned for 2022 [11].
Apr 19Filings 2022 or later [8].
Oct 18Filings now planned for 2021 at the earliest [7].
Oct 16Filings 2019 or later [4].
Jul 15EU and US filings will be 2018 or later [1].

Category

Immunotherapy, interferes with a protein called PD-L1 (Programmed Death-Ligand 1).
UK incidence of advanced NSCLC is 40 per 100,000.
Non-small cell lung cancer (NSCLC) - early stage adjuvant therapy
Intravenous

Further information

Yes

Trial or other data

Mar 21Genentech announced the PIII IMpower010 study met its primary endpoint of disease-free survival at interim analysis. Atezolizumab showed a statistically significant improvement in DFS in all Stage II-IIIA populations with the magnitude of benefit particularly pronounced in the PD-L1-positive population. Follow-up will continue with planned analyses of DFS in the overall intent-to-treat (ITT) population, which at the time of analysis did not cross the threshold, and overall survival (OS) data, which were immature at the time of interim analysis [11].
Oct 20PIII IMpower 010 is now due to complete collection of primary outcome data in Nov 21 [10].
Dec 19PIII IMpower 010 (NCT02486718) is due to complete collection of primary outcome data in Nov 20 [9].
Oct 18PIII IMpower 010 (NCT02486718) has finished recruitment; timescales unchanged [6].
Oct 16PIII IMpower 010 (NCT02486718) now due to complete collection of DFS data in Feb 26 [5].
Dec 15Companion diagnostic test also in development and will be required to identify suitable patients [3].
Sep 15PIII IMpower 010 (NCT02486718) study is recruiting from sites worldwide, including US & EU. Collection of primary outcome data is expected to complete in 2025 [2].
Jun 15First pt enrolled in PIII IMpower 010 study comparing atezolizumab with best supportive care in 845 patients, following adjuvant cisplatin-based chemotherapy. Disease-free survival is the primary outcome [1].

Evidence based evaluations

Tecentriq Ovarian, fallopian tube or peritoneal platinum-sensitive cancer - second-line after failure of bevacizumab and platinum chemotherapy

Information

Tecentriq
Licence extension / variation
Roche
Roche

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

Immunotherapy, interferes with a protein called PD-L1 (Programmed Death-Ligand 1)
In 2013 there were 7,284 new cases. In 2014 there were 4,128 deaths from ovarian cancer. It is the sixth most common cancer in women. 53% are diagnosed in women aged 65 years or older. Most cases are diagnosed at a late stage [1]
Ovarian, fallopian tube or peritoneal platinum-sensitive cancer - second-line after failure of bevacizumab and platinum chemotherapy
Intravenous infusion

TecentriqMetastatic cervical cancer - first- or second-line with bevacizumab, paclitaxel and platinum chemotherapy

Information

Tecentriq
Licence extension / variation
Roche
Roche

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Immunotherapy, interferes with a protein called PD-L1 (Programmed Death-Ligand 1). Dosed at 1200mg every 3 weeks.
There are around 3,200 new cervical cancer cases in the UK every year [1].
Metastatic cervical cancer - first- or second-line with bevacizumab, paclitaxel and platinum chemotherapy
Intravenous infusion

TecentriqAdvanced endometrial cancer - first-line with paclitaxel and carboplatin

Information

Tecentriq
Licence extension / variation
Roche
Roche

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
None

Category

Immunotherapy, interferes with with a protein called PD-L1 (Programmed Death-Ligand 1).
In the UK there are about 8,600 new cases per year [1].
Advanced endometrial cancer - first-line with paclitaxel and carboplatin
Intravenous infusion

TecentriqNon-small cell lung cancer (NSCLC) and all other Tecentriq indications - subcutaneous formulation

Information

Tecentriq
New formulation
Roche
Roche

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
None

Category

Immunotherapy, interferes with a protein called PD-L1 (Programmed Death-Ligand 1).
UK incidence of advanced NSCLC is 40 per 100,000.
Non-small cell lung cancer (NSCLC) and all other Tecentriq indications - subcutaneous formulation
Subcutaneous injection

TecentriqMalignant melanoma, BRAFv600 mutation-positive metastatic or unresectable locally advanced - first-line in combination with cobimetinib and vemurafenib

Information

Tecentriq
Licence extension / variation
Roche
Roche

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Dec 21Development of the NICE TA for this indication was previously suspended in Jan 20; assume company currently has no plans to develop this indication for the UK at this time [14].
Oct 21No plans for EU filing stated in company pipeline [15].
Jul 20US FDA approves atezolizumab in combination with cobimetinib and vemurafenib for the treatment of BRAF V600 mutation-positive advanced melanoma. The approval was based on the results from PIII IMspire 150 trial and following priority review. The review was also conducted under project orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology products among international partners [12].
May 20Filed in US [11].
Apr 20EU & US filings planned for 2019 [4].
Oct 19Filings will now be 2020 [6].
Oct 18Filings still on course for 2019 [5].
Mar 17PIII study has started [3].

Category

Immunotherapy, interferes with a protein called PD-L1 (Programmed Death-Ligand 1)
The UK incidence of malignant melanoma is about 21 per 100,000 people, and is doubling every 10-20 years. BRAF cancer-causing mutation occurs in about 50% of melanomas. Brain metastases are common in pts with cutaneous melanoma & associated with a poor prognosis. Surgery & radiotherapy may provide local control in pts with few metastases.
Malignant melanoma, BRAFv600 mutation-positive metastatic or unresectable locally advanced - first-line in combination with cobimetinib and vemurafenib
Intravenous

Further information

Yes

Trial or other data

Nov 20PIII IMspire150 TRILOGY is continuing to collect data and due to complete in Jul 23 [13].
Jun 20In the PIII IMspire150 study (n=514), the addition of atezolizumab to vemurafenib and cobimetinib was associated with prolonged progression-free survival (15.1 vs 10.6 months with vemurafenib plus cobimetinib [control]; HR 0.78; 95% CI 0.63-0.97; p=0.025) [10].
Apr 20Results of the PIII IMspire 150 TRILOGY study were presented virtually at the American Association for Cancer Research annual meeting. Adding atezolizumab to cobimetinib and vemurafenib decreased the risk of disease progression or death by 22% vs cobimetinib and vemurafenib alone. Patients on the triple combination went a median 15.1 months without their disease worsening, vs 10.6 months for those who didn’t receive atezolizumab as part of their treatment. Overall patients responded at a similar rate to both combinations, but responses lasted longer for those taking the triple combination, coming in at a median 21 months vs 12.6 months [9].
Dec 19Primary endpoint of improved PFS is met in PIII IMspire150 study [8].
Nov 19PIII IMspire 150 TRILOGY study (NCT02908672) finished collecting primary outcome data in Oct 19 [7].
Oct 18PIII IMspire 150 TRILOGY study (NCT02908672) enrolled the last patient in Q2 18 [5].
Nov 16Roche plans to initiate a randomised PIII trial to assess the safety, efficacy and pharmacokinetics of combination of atezolizumab, cobimetinib and vemurafenib in patients with previously untreated BRAFv600 mutation-positive metastatic or unresectable locally advanced melanoma (CO39262; NCT02908672). The double-blind trial anticipates enrolment of approximately 500 patients in Austria, Belgium, Israel, Netherlands and Switzerland. the study is due to start in Feb 17, and collection of primary outcome data (PFS) should complete Feb 2020 [2].
Nov 16Roche reports data from two PIb studies. In one study in 30 previously untreated patients with BRAF-positive melanoma, atezolizumab in combination with Cotellic and Zelboraf delivered an 83% response rate--or 24 patients--with a complete response in three of them. The regimen was well-tolerated; 40% of patients had side effects that resolved with appropriate interventions. In the other study in 22 melanoma patients who hadn’t previously been treated with a PD-1/PD-L1 drug, Tecentriq plus Cotellic performed in those with and without the BRAF mutation. The response rate was lower here--45% overall--but the study was long enough to generate some survival data. The combination held off cancer progression for 12 months, 15.7 months in the BRAF-positive patients and 11.9 months in the non-BRAF group [1].

Evidence based evaluations

TecentriqRenal cell carcinoma - adjuvant therapy

Information

Tecentriq
Licence extension / variation
Roche
Roche

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Jul 22Development discontinued; Tecentriq for adjuvant treatment of RCC no longer listed in Roche planned filings [10].

Category

Immunotherapy, interfers with with a protein called PD-L1 (Programmed Death-Ligand 1).
Renal cancers account for approximately 2-3% of all malignancies. In 2009, there were 9,286 new cases of kidney cancer in the UK: 5,706 (61%) in men and 3,580 (39%) in women, giving a male:female ratio of 16:10.
Renal cell carcinoma - adjuvant therapy
Intravenous

Further information

Yes

Trial or other data

Jul 22Roche announces that atezolizumab has failed in the PIII IMmotion010 trial [9].

Evidence based evaluations