dm+d

Unassigned

New Medicines

ContegoMalignant melanoma in patients who have progressed after anti-PD-1 therapy - monotherapy

Information

Contego
New molecular entity
Iovance Biotherapeutics
Iovance Biotherapeutics

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Yes
Nov 21Iovance received regulatory feedback from the FDA in May 21 regarding its potency assays for lifileucel. Following FDA feedback, it continued work developing and validating potency assays and engaged in discussions with the FDA during H2 21. Iovance expects to file a BLA submission for lifileucel in metastatic melanoma in H1 22. In connection with this BLA submission, the IRC is expected to independently assess responses for Cohort 4 patients through the data cut date, which must be completed prior to BLA submission or disclosure of IRC-read data [9].
May 21US FDA requests additional data on potency assays for this treatment which will delay filing. [8]
Mar 21Iovance have potential to file in US this year. They have completed clean room construction and anticipate commercial scale production by 2022 [6].
Oct 20Iovance provides an update on a recent Type B meeting with the FDA. It believe that clinical data from its C-144-01 trial supports the potential for lifileucel as a treatment for metastatic melanoma. Iovance and the FDA have reached agreement on the duration of follow up for its pivotal Cohort 4 to support the BLA submission. As part of the Type B meeting, the company and the FDA have not been able to agree on the required potency assays to fully define lifileucel, which is required as part of a BLA submission. The company is now continuing to refine the information from its current potency assays and simultaneously developing additional assays. Iovance has also come in agreement with the FDA regarding the amount of clinical follow up for the BLA, and will work closely with the FDA to reach alignment on its assays. This will delay the BLA submission from end of 2020 to 2021 [5].
Apr 20Iovance also reports that it began construction of a state-of-the-art, 136,000 square foot commercial-scale production facility in Philadelphia for its TIL therapies in Jun 19. The new facility is expected to be completed by year-end 2021 to support commercial supply in 2022 [4].
Apr 20Iovance reports in final year results that patient dosing in the pivotal cohort 4 of the C-144-01 study completed in Jan 20, three months ahead of schedule. Iovance intends to submit a biologics license application (BLA) to FDA subsequent to consultation with the agency in 2020 [4].
Apr 20US FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation for lifileucel in advanced melanoma based on data from the C-144-01 trial [3].
Apr 20Has orphan drug status and fast track status in US [3].
Oct 18Iovance Biotherapeutics announces completion of End of PII meeting with the US FDA. FDA acknowledged the potential acceptability of a single-arm cohort for registration. And that conduct of a randomized PIII trial may not be feasible in its intended population of advanced melanoma patients who have been treated with at least one systemic therapy including a PD-1 blocking antibody and if BRAF V600 mutation positive, a BRAF inhibitor or BRAF inhibitor with MEK inhibitor and is not required for initial registration of lifileucel. As a result, the company has decided to expand the ongoing C-144-01 trial with an additional cohort with a primary endpoint of overall response rate [3].

Category

Autologous ready-to-infuse product of tumour-infiltrating lymphocytes (TILs) isolated from a patient's own tumours. These therapeutic TILs are expanded in vitro to several billion cells before being infused, typically with a high dose of interleukin-2.
In 2011, the UK age-standardised incidence of melanoma for females was 17.6 (11.7 in 2001) and for males 17.5 (10.1 in 2001) per 100,000 population [1].
Malignant melanoma in patients who have progressed after anti-PD-1 therapy - monotherapy
Intravenous infusion

Further information

Yes

Trial or other data

Apr 21Company announces results of Cohort 2 in PII innovaTIL-01 trial. The pts had heavily pretreated metastatic melanoma with high baseline disease burden and had progressed to multiple prior therapies (3.3 mean). Lifileucel demonstrated a 36.4% overall response rate in this group. Among that rate were 4.5% complete responses and 31.8% partial responses. The median duration of response was not reached at the 28.1 month follow-up time. The adverse event profile was consistent with the underlying advanced disease, lymphodepletion and IL-2 regimens, with no additional adverse events emerging over time [7].
Mar 21PII innovaTIL-01 trial is due to complete collection of primary outcome data in Jul 21 [10].
Jan 20PII innovaTIL-01 trial is active but no longer recruiting [2].
Sep 15PII innovaTIL-01 trial to evaluate the safety and efficacy of lifileucel in patients with metastatic melanoma who have progressed on prior checkpoint targeted therapy starts (C-144-01; NCT02360579). Lifileucel is an autologous adoptive cell transfer therapy that utilizes a TIL manufacturing process, as originally developed by the NCI, for the treatment of patients with metastatic melanoma. The adoptive cell transfer therapy used in this study involves patients receiving a lymphocyte depleting preconditioning regimen, prior to infusion of autologous TIL, followed by the administration of a regimen of IL-2. 178 adults will be recruited in the US, France, Germany, Hungary, Italy, Spain, Switzerland and the UK; UK sites are Royal Marsden (London), Beatson West of Scotland Cancer Centre (Glasgow), Addenbrookes Hospital (Cambridge) and Sarah Cannon Research Institute (London). Primary outcome is objective response rate; collection of these data is due to complete Jul 20 [2].

Evidence based evaluations

ContegoRecurrent, metastatic or persistent cervical cancer

Information

Contego
Licence extension / variation
Iovance Biotherapeutics
Iovance Biotherapeutics

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Nov 20Iovance reports that the last patient was dosed in the pivotal Cohort 1 of the C-145-04 study of lifileucel, formerly LN-145, for metastatic cervical cancer. Plans for filing not discussed - presume this will not happen in 2020 as previously planned [9].
Apr 20US filing now planned by end of 2020 [8].
Apr 20Iovance reports that it began construction of a state-of-the-art, 136,000 square foot commercial-scale production facility in Philadelphia for its TIL therapies in Jun 19. The new facility is expected to be completed by year-end 2021 to support commercial supply in 2022 [8].
Jul 19Intention to file for Cervical cancer (Metastatic disease, Recurrent, Second-line therapy or greater) in second half of 2020 in US [6]
May 19Granted breakthrough therapy in US [6].
Feb 19Granted fast track designation in the US for treatment of patients with recurrent, metastatic or persistent cervical cancer who have progressed while on or after chemotherapy [4].
May 18Iovance Biotherapeutics granted orphan-drug designation by the US FDA for autologous tumour infiltrating lymphocytes for treatment of cervical cancer with a tumour size of greater than 2cm in diameter [4].
Sep 17Iovance intends to use the data from PII trials to support global registration for LN-145 [5].

Category

Autologous cell therapy consisting of tumour-infiltrating lymphocytes (TIL) isolated from the patient tumour, that are expanded ex vivo, and infused back into the patient followed by interleukin-2 (IL-2) administration
There were 3,126 new cases of cervical cancer in 2015 in the UK [1]. Around 30% of cervical cancers are detected through cervical screening in the UK. Cervical cancer is more common in those aged 25-34 years [2].
Recurrent, metastatic or persistent cervical cancer
Intravenous infusion

Further information

Yes

Trial or other data

Nov 21Iovance explains that in PII trial (C-145-04, NCT03108495) that Cohort 2 had completed enrolment in Jan 21 and that data from this cohort may be supportive of registration because of the expected changing landscape of care for cervical cancer patients. For example, the potential shift from chemotherapy in front-line followed by pembrolizumab in second-line cervical cancer to the use of pembrolizumab in combination with chemotherapy in first-line cervical cancer, as well as the approval of TIVDAK in the U.S. for the treatment of adults with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Iovance intends to initiate a dialogue with the FDA to discuss these cohorts and potential BLA submission plans for lifileucel in cervical cancer after resolution of regulatory discussions regarding its potency assays [12].
Jun 21PII innovaTIL-04 study (NCT03108495) is still recruiting [11].
Nov 20PII innovaTIL-04 study (NCT03108495) continues to recruit and required sample size has increased again to 138. Collection of primary outcome data now expected to complete Dec 21 [10].
Dec 19UK trial sites: NCT03108495 (Bristol, UCL, Glasgow) [3].
Nov 19Iovance reports that, in order to position LN-145 for potential future use in broader lines of therapy in cervical cancer, it amended the C-145-04 trial to collect additional data on early line patients as well as later-line patients. Enrolment in these additional cohorts is not expected to impact the timing of the completion of Cohort 1. As a result of these changes, we have also expanded the sample size of the C-145-04 clinical trial to include 138 patients from the appropriate patient populations across these five cohorts. We plan on completing enrollment into Cohort 1 of C-145-04 at approximately mid-year 2020 [8].
Apr 19PII innovaTIL-04 study (NCT03108495) is recruiting. Collection of primary outcome data (objective response rate) is due to complete Mar 20 [3].
Apr 19Iovance increases the sample size to 59 in PII study (NCT03108495). In addition, the primary endpoint of objective response rate (ORR) is modified to be determined by a Blinded Independent Review Committee (BIRC). The amendments were made in anticipation of a planned meeting with the US FDA to discuss the registration pathway for LN-145 in cervical cancer. A number of other changes have been made including newly enrolled patients to be treated using tumour-infiltrating lymphocytes produced from the Gen 2 manufacturing process, & to limit the number of prior therapies to no more than three and to exclude patients who have been treated with prior immunotherapy [4]
Apr 17PII trial to evaluate the safety, tolerability and efficacy of LN-145, followed by interleukin-2, in patients with recurrent and/or metastatic cervical cancer starts (C-145-04; innovaTIL-04; NCT03108495). 47 patients will be recruited in the US, Spain and UK [3].

ContegoMalignant melanoma in patients naïve to anti-PD-1 therapy - in combination with pembrolizumab

Information

Contego
Licence extension / variation
Iovance Biotherapeutics
Iovance Biotherapeutics

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials

Category

Ready-to-infuse product consisting of tumour-infiltrating lymphocytes (TILs) isolated from a patients own tumours. These therapeutic TILs are expanded in vitro to several billion cells before being infused, typically with a high dose of interleukin-2.
Variable depending on tumour type.
Malignant melanoma in patients naïve to anti-PD-1 therapy - in combination with pembrolizumab
Intravenous infusion

Trial or other data

Nov 21PII basket trial, IOV-COM-202, is still recruiting; timescales unchanged [4].
Jun 21Updated data from Cohort 1A of the PII IOV-COM-202 trial showed that lifileucel in combination with pembrolizumab resulted in a high Overall Response Rate (ORR) and favourable Complete Response Rate in Immune Checkpoint Inhibitor (ICI) naïve advanced melanoma patients. Initial seven patients showed three Complete Responses (CR), three Partial Responses (PR) and one best response of Stable Disease (SD). Previous early data suggested the response rate of lifileucel plus pembrolizumab may be additive. Cohort 1A in the IOV-COM-202 trial evaluated lifileucel in combination with pembrolizumab in patients who are naïve to ICI, or anti-PD-1, therapy. Initial patients (n=7) enrolled in Cohort 1A had high tumor burden at baseline, and 71.4% had not received any prior systemic therapy. Six of the seven patients had a confirmed objective response (OR), representing an 86% ORR [2 complete responses (CR), 1 unconfirmed CR (uCR) who had not yet reached the confirmatory CR assessment, and 3 partial responses (PR)], with one best response of stable disease. ORR was investigator-assessed per RECIST 1.1. Responses deepened over time and the CR/uCR rate was 43%. Median follow up was 8.2 months. As at May 2021, all ongoing responses continued [3].
May 21PII basket trial, IOV-COM-202, is recruiting [1].
May 19PII trial to evaluate lifileucel or LN145 in combination with pembrolizumab for the treatment of solid tumours (NSCLC, melanoma, HNSCC) starts (IOV-COM-202; EudraCT2018-001608-12; NCT03645928). The open-label, multi-cohort, non-randomised, multicentre trial will enrol 135 patients in the US, Canada, France, Germany, Greece, Spain, Switzerland and the UK (sites Guy ´s Hospital in London, and Bristol Haematology and Oncology Centre in Bristol). Co-primary endpoints for each cohort are objective response rate (ORR) per RECIST 1.1 and safety (grade ≥ 3 TEAE). Lifileucel will be administered to Cohort 1A in combination with pembrolizumab and to cohort 1C as a single agent. Collection of primary outcome is due to complete Dec 23 [1,2].