dm+d

Unassigned

New Medicines

Squamous or non-squamous non-small cell lung cancer (NSCLC) - second- or third-line

Information

New molecular entity
Novartis
Novartis

Development and Regulatory status

None
Pre-registration (Filed)
None
Apr 22EMA validates MAA for regulatory review for tislelizumab as monotherapy for the treatment of locally advanced or metastatic NSCLC after prior chemotherapy in adults [4]

Category

A humanised IgG4, anti-PD-1 monoclonal antibody. It has a differently engineered Fc region from approved PD-1 antibodies, to minimise negative interactions with other immune cells.
UK incidence of NSCLC is 15 to 30 per 100,000 people. Non-small cell lung cancer (NSCLC) accounts for 80%–90% of lung cancers and 42% of NSCLC are squamous [1,2].
Squamous or non-squamous non-small cell lung cancer (NSCLC) - second- or third-line
Intravenous infusion

Trial or other data

May 21III study (NCT03358875) is active but no longer recruiting [3].
Nov 17 PIII trial to show that BGB-A317 will improve overall survival in participants with Stage IIIB or IV non-small cell lung cancer when compared to docetaxel in second or third-line treatment setting starts (NCT03358875). 805 adults with histologically confirmed, locally advanced or metastatic squamous or non-squamous NSCLC who have disease progression during or after a platinum-containing regimen will be recruited in countries including China, Brazil and Europe (not UK). Patients will be randomised to BGB-A317 (tislelizumab) 200mg IV 3-weekly or docetaxel 75mg/m2 IV three-weekly. Primary outcome is overall survival; collection of these data is due to complete Dec 21

Evidence based evaluations

Advanced, unresectable and metastatic squamous cell oesophageal cancer - second-line

Information

New molecular entity
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
Yes
Yes
Apr 22EMA validates MAA for regulatory review for tislelizumab for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy [12]
Sep 21US FDA accepts BLA with a PDUFA date of 12/7/21 [11].
Jul 21Has orphan drug status in EU and US for treatment oesophageal cancer [9,10].
Jan 21Novartis is collaborating with BeiGene on further development of tislelizumab. Novartis will have commercialisation rights in the US, EU and Japan although BeiGene retains an option to help with North American commercialization [6].
Jun 19BeiGene and Celgene Corporation will terminate their global collaboration for tislelizumab, with BeiGene continuing further development [4].

Category

A humanised IgG4, anti-PD-1 monoclonal antibody. It has a differently engineered Fc region from approved PD-1 antibodies, to minimise negative interactions with other immune cells.
Oesophageal cancer is the 14th most common cancer in the UK, with an estimated 8,919 new diagnoses in the UK each year. It is often diagnosed at an advanced stage, with around 70-80% diagnosed at stage 3 (locally advanced) or 4 (metastatic) [1].
Advanced, unresectable and metastatic squamous cell oesophageal cancer - second-line
Intravenous

Further information

Yes

Trial or other data

Apr 22Results of PIII RATIONALE 302 trial reported in Journal of Clinical Oncology [13].
Jun 21 Novartis announce PIII RATIONALE 302 trial showed that tislelizumab improved OS vs chemotherapy (median 8.6 vs 6.3 months; HR=0.70[95% CI 0.57-0.85]) [8].
Jan 21BeiGene announces PIII RATIONALE 302 trial (n=512) meets primary endpoint [7].
Jun 20PIII trial (NCT03430843) is ongoing and due to complete collection of primary outcome data s planned in Sep 20. It completed recruitment in March and also enrolled patients from the UK and Europe [7].
Dec 19PIII trial (NCT03430843) is recruiting [5].
Dec 18PIII trial (NCT03430843) is recruiting [3].
Jan 18PIII trial to compare safety and efficacy of 200mg tislelizumab, with investigator-chosen chemotherapy (paclitaxel, docetaxel, or irinotecan) as a second-line treatment in patients with advanced, unresectable and metastatic oesophageal squamous cell carcinoma starts (NCT03430843). The primary endpoint of the trial is overall survival, and secondary endpoints are progression-free survival, objective response rate, duration of response, health-related quality of life, safety, and tolerability. 450 patientswill be enrolled in the US, China & Japan. Collection of primary outcome data is due to complete Sep 20 [2].

Evidence based evaluations

Non-squamous non-small cell lung cancer (NSCLC) - first-line in combination with chemotherapy

Information

Licence extension / variation
Novartis
Novartis

Development and Regulatory status

None
Pre-registration (Filed)
None
Apr 22EMA validates MAA for regulatory review for tislelizumab for the first-line treatment of locally advanced or metastatic non-squamous NSCLC in adults whose tumors have no EGFR or ALK positive mutations in combination with pemetrexed and platinum-containing chemotherapy [8]
May 21Filings planned for 2021 [6].
Jan 21Novartis is collaborating with BeiGene on further development of tislelizumab. Novartis will have commercialisation rights in the US, EU and Japan although BeiGene retains an option to help with North American commercialisation [5].
Jun 20Data from the RATIONALE-304 study filed in China [4].
Jun 19BeiGene and Celgene Corporation will terminate their global collaboration for tislelizumab, with BeiGene continuing further development.[3]

Category

A humanised IgG4, anti-PD-1 monoclonal antibody. It has a differently engineered Fc region from approved PD-1 antibodies, to minimise negative interactions with other immune cells.
In 2016, approximately 32,500 people were diagnosed with NSCLC in England, and around 61% had stage IIIB or stage IV disease. Approximately 70% of NSCLC are of non-squamous histology and can be either large-cell undifferentiated carcinoma or adenocarcinoma [1].
Non-squamous non-small cell lung cancer (NSCLC) - first-line in combination with chemotherapy
Intravenous

Trial or other data

Oct 21PIII RATIONALE-304 study has finished recruiting, after enrolling 334 participants. Collection of primary outcome data now expected to complete Dec 21 [7].
Sep 20Beigene presents updated results from PIII RATIONALE-304 trial. Tislelizumab met its primary endpoint of progression-free survival in a pre-determined interim analysis with no new safety signal, in patients with stage IIIB or IV non-squamous NSCLC (NCT03663205; BGB-A317-304). The safety profile was consistent with the known risks of each study treatment. The open-label trial completed enrolment of 334 patients in China [4].
Jul 18PIII RATIONALE-304 study in patients with stage IIIB or IV non-squamous NSCLC starts (NCT03663205; BGB-A317-304). The trial will investigate the efficacy and safety of tislelizumab combined with platinum-pemetrexed versus platinum-pemetrexed alone as first-line treatment for patients with stage IIIB or IV disease, with no EGFR mutations or ALK translocations. The open-label trial will enrol 334 patients in China [2].

Squamous non-small cell lung cancer (NSCLC) - first-line in combination with chemotherapy

Information

Licence extension / variation
Novartis
Novartis

Development and Regulatory status

None
Pre-registration (Filed)
None
Apr 22EMA validates MAA for tislelizumab for the first-line treatment of locally advanced or metastatic squamous NSCLC in adults in combination with carboplatin and either paclitaxel or nab-paclitaxel [11]
Nov 21Novartis now plans a H1 2022 MAA submission, and is evaluating US BLA submission options [10].
May 21Novartis plans filings in 2021 [9].
Jan 21Tislelizumab receives approval from the China National Medical Products Administration for use in combination with chemotherapy regimens (either paclitaxel and carboplatin or nab-paclitaxel and carboplatin) as a first-line treatment for patients with advanced squamous NSCLC. The approval was based on the results from the PIII RATIONALE-307 trial [7].
Jan 21Novartis is collaborating with BeiGene on further development of tislelizumab. Novartis will have commercialisation rights in the US, EU and Japan although BeiGene retains an option to help with North American commercialization [5].
Jun 20PIII trial underway in China. [3]

Category

A humanised IgG4, anti-PD-1 monoclonal antibody. It has a differently engineered Fc region from approved PD-1 antibodies, to minimise negative interactions with other immune cells.
UK incidence of NSCLC is 15 to 30 per 100,000 people. Non-small cell lung cancer (NSCLC) accounts for 80%–90% of lung cancers and 42% of NSCLC are squamous [1,2].
Squamous non-small cell lung cancer (NSCLC) - first-line in combination with chemotherapy
Intravenous

Trial or other data

Apr 21PIII RATIONALE-307 trial (NCT03594747) is published; in this study in China (n=355), the addition of tislelizumab to chemotherapy (paclitaxel and carboplatin) was associated with improved progression-free survival in patients with advanced squamous non–small-cell lung cancer (7.6 v 5.5 months; p<0.001) [8].
Jul 20PIII RATIONALE-307 trial (NCT03594747) is due to complete collection of primary outcome data in Mar 21 [6].
Jan 20Pivotal PIII BeiGene trial (NCT03594747) in China met its primary endpoint of improved progression-free survival (PFS) at the planned interim analysis. Pts with previously untreated advanced squamous NSCLC (n= 360) were randomised 1:1:1:1 to receive tislelizumab (200mg every three weeks) with paclitaxel and carboplatin or tislelizumab with nab paclitaxel (Celgene’s Abraxane) and carboplatin or placlitaxel and carboplatin alone. Pts on chemotherapy-only were eligible to cross over to receive tislelizumab monotherapy. Both tislelizumab treatment arms of the trial met the primary end point at interim analysis - only top line data were presented. The safety profile of tislelizumab was consistent with the known risks of each study treatment, and no new safety signals were identified. [3,4]

Advanced hepatocellular carcinoma (HCC) - first-line

Information

New molecular entity
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes

Category

A humanised IgG4, anti-PD-1 monoclonal antibody. It has a differently engineered Fc region from approved PD-1 antibodies, to minimise negative interactions with other immune cells.
The age-standardised incidence rate for liver cancer in the UK in 2008 was 4.3 per 100,000 population [1].
Advanced hepatocellular carcinoma (HCC) - first-line
Intravenous

Further information

Yes

Evidence based evaluations

Gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma - first-line

Information

Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

A humanised IgG4, anti-PD-1 monoclonal antibody. It has a differently engineered Fc region from approved PD-1 antibodies, to minimise negative interactions with other immune cells.
Oesophago-gastric cancer has become steadily more common in the last 30 years. Around 13,000 people are newly diagnosed each year – 9 in 10 of these are aged over 50 [1].
Gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma - first-line
Intravenous

Advanced, unresectable and metastatic squamous cell oesophageal cancer - first-line

Information

Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

A humanised IgG4, anti-PD-1 monoclonal antibody. It has a differently engineered Fc region from approved PD-1 antibodies, to minimise negative interactions with other immune cells.
Oesophageal cancer is the 14th most common cancer in the UK, with an estimated 8,919 new diagnoses in the UK each year. It is often diagnosed at an advanced stage, with around 70-80% diagnosed at stage 3 (locally advanced) or 4 (metastatic) [1].
Advanced, unresectable and metastatic squamous cell oesophageal cancer - first-line
Intravenous

Further information

Yes

Evidence based evaluations