Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as REGN2810, Arm 1 cemiplimab, Cemiplimab-Rwlc
Cemiplimab · 46 trials · 63 indications
For patients who do not have a tumor recurrence or death, DFS will be censored on the date of last disease assessment.
OS was defined as the time from randomization to the date of death due to any cause.
OS was defined as the time from randomization to the date of death due to any cause.
Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.
Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.
PFS as assessed by blinded IRC per RECIST 1.1 was defined as the time from randomization to the date of the first documented tumor progression, or death due to any cause, whichever occurred earlier.
Successful conversion to resectable disease must meet all of the following criteria: * Absence of extra-regional lymph node metastases, including retropancreatic or paraceliac lymph node involvement * Absence of invasion of the portal vein or main hepatic artery * Absence of extrahepatic organ tumor invasion, except for contiguous involvement of the diaphragm * Absence of bilobar liver involvement, including bilateral bile duct involvement to the secondary radicles * If right or left hepatic lobe atrophy, absence of contralateral secondary biliary radicle involvement * Absence of disseminated metastatic disease * Adequate estimated liver remnant after surgery (This may be achieved with portal vein embolization.) * Tumor resected.
Measured by the proportion of patients completing surgery within 60 days after Day 1 of treatment with cemiplimab and fianlimab
The frequency and severity of adverse events, according to NCI CTCAE V6.0
To evaluate the overall survival of participants with metastatic pancreatic adenocarcinoma harboring SWI/SNF alterations treated with cemiplimab in combination with gemcitabine as a second-line treatment.
Pathologic complete response (pCR): 0% viable tumor in primary tumor and resected lymph nodes.
The primary endpoint is 6-month disease control rate (DCR). The analysis will be conducted in the FAS population. DCR is defined as the proportion of patients who have achieved at 6 months an overall response of CR, PR or stable disease (SD), as assessed by an independant review committee (IRC) per RECIST v1.1 modified for mesothelioma.
Comparison of the 1-year progression-free survival between patients with oligo-metastatic ccRCC treated with cemiplimab alone versus those treated with both cemiplimab and fianlimab following SBRT.
Rate of clinical complete response after 4 cycles of neoadjuvant chemoimmunotherapy. Complete clinical response will be defined as: * No high-grade malignancy on repeat TURBT * No malignant cells on urine cytology * No definitive evidence of invasive local or metastatic disease on cross-sectional imaging (CT chest, abdomen, and pelvis with contrast or, if renal dysfunction, MRI with contrast) Cytoscopy and imaging should occur within 4 weeks of end of neoadjuvant therapy.
Defined by responders at surgery using clinical assessment and RECIST v1.1. Results will be summarized with frequency counts, percentages, and exact Clopper-Pearson 95% CIs. Tumor response will follow RECIST v1.1: up to five target lesions (max two per organ) measured by longest diameter (non-nodal) or short axis (nodal). Complete Response is disappearance of all target lesions and lymph nodes \<10 mm. Partial Response is ≥30% decrease from baseline. Progressive Disease is ≥20% increase (and ≥5 mm growth) from the smallest on-study sum or the appearance of new lesions. Stable Disease applies when changes do not meet PR or PD. Reasons for unevaluable cases will be documented.
Defined responders plus stable disease using clinical assessment and RECIST v1.1. Results will be summarized by frequency counts, percentages, and exact Clopper-Pearson 95% CIs. Tumor response will follow RECIST v1.1: up to five target lesions (no more than two per organ) measured by longest diameter (non-nodal) or short axis (nodal). Complete Response is disappearance of all target lesions and lymph nodes \<10 mm. Partial Response is ≥30% decrease from baseline. Progressive Disease is ≥20% increase (and ≥5 mm growth) from the smallest on-study sum or new lesions. Stable Disease applies when changes do not meet PR or PD. Reasons for unevaluable cases will be documented.
Complete response is defined as the disappearance of all lesions. Partial response is defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions.
The percentage of subject achieving undetectable PSA levels at 6 months after the combination will use measured to determine safety and activity of combined hormonal chemoimmunotherapy.
Time from first cemiplimab administration to disease recurrence/progression as per RECIST 1.1, fatal TRAEs or NSCLC-related death.
Composite Response Criteria integrates radiology findings \[Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\] and external lesion assessments from digital photography \[modified World Health Organization (WHO) criteria\].
ORR is defined as the proportion of patients with Complete Response (CR) or Partial Response (PR). ORR will be assessed according to RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
MPR is defined as ≤ 10% viable tumor cells in resected tumor after complete evaluation in the resected lung cancer specimen as determined by central pathology review and described by IASLC 2020 assessment criteria. The measure of interest is the proportion of treated patients with ≤ 10% residual viable tumor cells within all resected tissue as confirmed by the central pathology review.
PFS6 as defined from the time of treatment start to the time of progression (based on clinical assessment and imaging per Immunotherapy Response Assessment in Neuro-Oncology (iRANO)) or death, whichever is earlier, or last follow-up if neither progression nor death event is observed. PFS6 will be estimated as the empirical PFS probability at Month 6 using the Kaplan-Meier method.
OS as defined from the time of treatment start to the time of death or last follow up if surviving; OS-18 is further estimated as the empirical OS probability at Month 18 using the Kaplan-Meier method.
Contrast enhanced brain MRI and/or color digital photography will be performed baseline and every 8 weeks (+/-1 week) up to 12 months and according to standard practice thereafter until disease progression, independently of the end of treatment (except for documentation of disease progression).
Proportion of patients with a best overall response of confirmed complete response (CR) or partial response (PR)
Percentage of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through disease progression, by investigator review based on RECIST version 1.1
Cohorts A1, A2, A3
Cohort B, B2, B3
Cohort C
ORR was defined as percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 assessed as per ICR assessment. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm) (\< 1 centimeter \[cm\]). PR: At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. ORR was determined by Clopper-Pearson method.
ORR was defined as percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). For participants with metastatic disease, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) \<1 (centimeter (cm). -PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Clinical Response Criteria: -CR: All target and nontarget lesion(s) no longer visible, maintained for at least 4 weeks and no new lesions. -PR: Decrease of at least 50% in the sum the products of perpendicular longest dimensions of target lesion(s), maintained for at least 4 weeks and no new lesions.
Progression-free survival, defined as the number of days from the start date of Y90 treatment (administered two times) to the date of progression, relapse, or death.
The incidence of DLTs evaluated in Phase Ib: considered as the rate of patients who experience adverse events (AE) and treatment-related AEs (TRAEs) assessed by NCI CTCAE v5.0 which may be considered DLTs.
Relapse-Free Survival (RFS) rate at 3 years evaluated in Phase II study. 3-years RFS rate is defined as the percentage of patients free of locoregional progression or recurrence or new basocellular tumors, distant metastasis (RECIST v 1.1) or death due to any cause after 3 years from the date of study treatment. Patients not presenting any of the previous events will be censored at the date of last assessment. RFS will be summarized using the Kaplan-Meier method and displayed graphically where appropriate. The Cox proportional hazards model will be fitted to compute the hazard ratios on potential stratified groups if applicable. RFS will be calculated as median / mean (95% CI) for each cohort and RFS rate for different timepoints as applicable.The primary endpoint will be assessed locally and centrally. Central assessment will be prioritized for the primary endpoint.
The dose-limiting toxicity (DLT) will be the basis for safety and toxicity of Cemiplimab -TP that will be measured and reported only during the first cycle of Cemiplimab -TP for the first 6 study objects in each cohort A and B since the majority of the DLT occurs after the first treatment cycle in multiple phase I oncology clinical trials. DLTs must be related to a study drug, cemiplimab. Known and expected chemotherapy (TP, standard of care) adverse events not related to cemiplimab will not be defined as DLTs.
primary endpoint for Cohort 1 will be determination of the MTD/RP2D of ASP8374 when administered with cemiplimab among recurrent malignant glioma participants.
CD8+ TIL density from tumors obtained from participants randomized to the neoadjuvant study arm (2A) will be compared to tumor CD8+ TIL density obtained from control participants enrolled on Arm 2B who do not receive neoadjuvant therapy.
The pathological complete response will be estimated for each arm and reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method. Formal comparisons between arms will be conducted using Fisher's exact test. Participants in this study with unknown pathological response will be treated as non-responders in the primary analysis.
The MRD rate will be estimated for each arm and reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method. Formal comparisons between arms will be conducted using Fisher's exact test. Participants in this study with unknown pathological response will be treated as non-responders in the primary analysis.
Adverse events will be evaluated using the most recent version of the Common Terminology Criteria for Adverse Events (CTCAE).
Toxicity rates (grade 2, grade 3, grade 4, grade ≥ 2, grade ≥ 3, etc.) will be calculated for each study arm and reported along the corresponding 95% confidence intervals. The 95% confidence intervals will be constructed using the Wilson score method.
The proportions of patients who have observed GVHD in Cohort 1 or renal transplant rejection in Cohort 2. Participants will be evaluable for from the time of their first treatment.
Part 1a
Part 1a
Part 1a
Phase 1a/1b Determination of the feasibility of manufacturing 27T51 is measured by the percent of leukapheresis products collected that are able to be manufactured and released for infusion.
Phase 1b
Dose levels 1-3
Dose levels 1-3
MTD/MFD of Pexa-Vec administered by IV infusion in combination with Cemiplimab
Safety will be determined by assessing the severity and frequency of adverse events and laboratory toxicity using CTCAE v4.03
Evaluate anti-tumor activity and efficacy of IV or IT Pexa-Vec combined with IV Cemiplimab with respect to overall response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Peak serum concentration
Time to Cmax
Drug concentration in serum at the end of a dosing interval
AUC over a 3-week dosing interval
Observed terminal half-life
| Arm | Type | Description |
|---|---|---|
| Experimental Arm | EXPERIMENTAL | - |
| Control Arm | OTHER | - |
| Cemiplimab | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Chemo | OTHER | Part 1: Chemotherapy |
| REGN2810+Chemo Part 1 | EXPERIMENTAL | Part 1: REGN2810+chemo |
| REGN2810+AbbrevChemo+ipi | EXPERIMENTAL | Part 1: REGN2810+abbrev chemo+ipi |
| Placebo+Chemo | EXPERIMENTAL | Part 2: Placebo plus chemo |
| REGN2810+Chemo Part 2 | EXPERIMENTAL | Part 2: REGN2810+chemo |
| Experimental Therapy | EXPERIMENTAL | Cemiplimab |
| Control Therapy | ACTIVE_COMPARATOR | Investigator choice (IC) chemotherapy |
| Standard-of-care chemotherapy | ACTIVE_COMPARATOR | Standard-of-care chemotherapy will administered from these options: Doses of Paclitaxel + cisplatin OR Doses Paclitaxel + carboplatin OR Doses Gemcitabine + cisplatin or Doses Gemcitabine + carboplatin OR Doses Pemetrexed + cisplatin followed by optional pemetrexed maintenance OR Doses Pemetrexed + carboplatin followed by optional pemetrexed maintenance |
| Cemiplimab in combination with Fianlimab | EXPERIMENTAL | All patients will be treated with fianlimab 1600 mg IV plus cemiplimab 350 mg IV on Days 1 and 22. |
| Cemiplimab Plus Gemcitabine | EXPERIMENTAL | Combination therapy of cemiplimab plus gemcitabine. Cemiplimab will be supplied as 350 mg vials for intravenous administration at 3 mg/Kg every 2 weeks. Gemcitabine will be administered intravenously per standard of care at 1000mg/m\^2 on days 1, 8, 15 of every 28-day cycle. Cemiplimab plus gemcitabine will be administered until disease progression or other reasons that warrant discontinuation. |
| Cemiplimab plus chemotherapy | EXPERIMENTAL | cemiplimab given with standard of care chemotherapy for 4 treatments/cycles before surgery and then every 3 weeks for 1 year after surgery. |
| Arm A: cemplimab + chemotherapy | OTHER | cemplimab 350mg administered every 3 weeks for up to 24 months, with pemetrexed 500 mg/m² + platinum salt (cisplatin 75 mg/m² or carboplatin AUC 5) for 6 cycles of 21 days. |
| Arm B: cemplimab + fianlimab + chemotherapy | EXPERIMENTAL | cemplimab 350mg and fianlimab 1600mg administered every 3 weeks for up to 24 months, with pemetrexed 500 mg/m² + platinum salt (cisplatin 75 mg/m² or carboplatin AUC 5) for 6 cycles of 21 days. |
| Cemiplimab + Fianlimab | EXPERIMENTAL | Cemiplimab, 350 mg, IV, and Fianlimab 1600 mg, IV, q3w for 1 year. Patients will undergo treatment with the study drug(s) every 3 weeks for a maximum of 17 cycles (approximately 12 months) or until disease recurrence, unacceptable toxic effects, or intercurrent illness preventing further administration. |
| Group 1: Gemcitabine/Cisplatin/Cemiplimab | EXPERIMENTAL | * Gemcitabine 1000 mg/m\^2 IV (days 1 and 8 of 21 day for 4 cycles) * Cisplatin 70 mg/m\^2 IV (day 1 of 21 day cycle for 4 cycles) or renally-dosed split-dose -cisplatin 35 m/m\^2 IV (day 1 and 8 of 21 day cycle for 4 cycles) * Cemiplimab (REGN 2810) 350 mg IV every 3 weeks (17 cycles) |
| Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab | EXPERIMENTAL | * Gemcitabine 1000 mg/m2 IV (days 1 and 8 of 21 day cycle for 4 cycles) * Cisplatin 70 mg/m2 IV (day 1 of 21 day cycle for 4 cycles) or renally-dosed split-dose cisplatin 35 m/m2 IV (day 1 and 8 of 21 day cycle for 4 cycles ) * Cemiplimab (REGN 2810) 350mg IV every 3 weeks (4 cycles) * Fianlimab (REGN3767) 1600mg IV every 3 weeks (4 cycles) |
| Cohort 1: Cemiplimab | EXPERIMENTAL | Patients will undergo 2 infusions of Cemiplimab (Cemi), 350 mg every 3 weeks. Patients undergo CT or MRI scans and collection of blood samples throughout the trial. Patients also undergo biopsies during screening and on study. The recommended dose of Cemiplimab is 350 mg as an intravenous infusion over 30 minutes every 3 weeks (constituting one cycle). Dosing will occur in this manner for a single dose of 350mg Cemiplimab every 3 weeks constituting 1 cycle of therapy. Patients will undergo at least 2 cycles of Cemiplimab and at most, 4 additional cycles dependent upon treatment response. |
| Cohort 2: Fianlimab + Cemiplimab | EXPERIMENTAL | Patients will undergo infusions of Cemiplimab (C) and Fianlimab (F), 350 mg Cemiplimab + 1600 mg Fianlimab every 3 weeks. Fianlimab in combination with cemiplimab can be administered to patients in a sequential order through co-administration, or concurrently via a fixed-dose combination (FDC). When the FDC is used, the drug product containing co-formulated drugs in a vial is injected into the IV bag and delivered intravenously to the patient. FDC of fianlimab 1600 mg + cemiplimab 350 mg will be administered as a single infusion over 30 to 40 minutes every 3 weeks (constituting one cycle). Patients will undergo at least 2 cycles of the FDC and at most, 4 additional cycles dependent upon treatment response. |
| Motixafortide, Cemiplimab, Gemcitabine, Nab-Paclitaxel | EXPERIMENTAL | Participants will receive standard FDA-approved doses of gemcitabine and nab-paclitaxel for pancreas cancer and cemiplimab at the dose that is approved for participants with skin cancer. Participants will also receive motixafortide at a dose that has been deemed safe in previous studies when used in combination with immunotherapy and chemotherapy. If the combination study treatment causes a serious side effect in participants, the study treatment will be modified. |
| ADT Followed by Chemoimmunotherapy | EXPERIMENTAL | REGN2810 followed by chemoimmunotherapy: Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months. Week 4 start cemiplimab (REGN 2810) 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease. Week 10 start docetaxel 75 mg/m2 every 21 days for up to 6 cycles. |
| Three cycles of cemiplimab | ACTIVE_COMPARATOR | Three cycles of cemiplimab |
| Arm A | EXPERIMENTAL | - |
| Arm B | EXPERIMENTAL | - |
| Arm C | EXPERIMENTAL | - |
| Subsequent Therapy Arm | EXPERIMENTAL | - |
| Standard immunosuppression + Cemiplimab + Cetuximab (optional) | EXPERIMENTAL | Patients will receive standardized immunosuppression (sirolimus and prednisone) lead-in treatment for 7 to 14 days prior to starting treatment with cemiplimab. Cemiplimab is given IV on Day 1 of every 21-day cycle for a maximum of 24 months. Sirolimus is continued during cemiplimab, and dynamic prednisone is continued for the first 6 cycles. If patient progresses during treatment with cemiplimab, patients will be offered cetuximab as salvage therapy at the investigator's discretion and will be administered according to standard of care (SOC). |
| Treatment with Cemiplimab | EXPERIMENTAL | Cemiplimab 350 mg IV administered every 3 weeks Will be given for at least 3 pre-operative doses, with potential 4th dose pending interim radiographic assessment after cycle 2 of treatment. |
| Experimental Arm: LiTT + Cemiplimab | EXPERIMENTAL | Patients in the Experimental Arm will receive adjuvant cemiplimab (at a dose of 350 mg intravenously (IV)) every 3 weeks after LiTT for a maximum total of 36 months (or until disease progression or intolerable adverse event). The first adjuvant dose of cemiplimab must be given within 14 days post-LiTT. |
| Control Arm: LiTT + adjuvant chemotherapy | ACTIVE_COMPARATOR | Patients in the Control Arm will undergo LiTT, then will receive adjuvant chemotherapy (chosen by their treating physician) for up to 12 months as per standard of care (SOC), starting within 14 days post-LiTT. |
| Combination of MaaT033 + Cemiplimab (CB) | EXPERIMENTAL | CB will be administered every 3 weeks. Oral pooled fecal microbiotherapy MaaT033 will be taken by patient (capsules) for a week before CB administration, repeated every other 3 weeks for 6 months. |
| Best Investigator's Choice (BIC) | ACTIVE_COMPARATOR | Patients will receive chemotherapy according to current standard of care protocols according to investigator's best choice from current guidelines combinations. |
| Encorafenib+biNimetinib followed Cemiplimab+Fianlimab in BRAF mutated melanoma and brain metastses | EXPERIMENTAL | Patients with BRAF mutant melanoma and symptomatic brain metastases will treatment with encorafenib plus binimetinib followed by cemiplimab and fianlimab Induction treatment with oral encorafenib 450 mg once daily (QD) + binimetinib 45 mg twice daily (BID)(combination: EB) for approximately two months (i.e. 8 weeks) followed by cemiplimab 350 mg + fianlimab 1600 mg combination every 3 weeks (Q3W)(Combination: CF) administered to patients intravenously (IV) for up to two years. Treatment may be discontinued due to death, PD or non-acceptable toxicity. Encorafenib plus binimetinib should be discontinued at least 72 hours prior to the first dose of cemiplimab plus fianlimab. Rechallenge with encorafenib 450mg QD + binimetinib 45 mg BID will be mandatory for those patients that progress under CF, with the exception of patients with intracranial response or stabilization and only extracranial PD in which case CF could be continued at the physician criteria. In the case of continuing treat |
| Chemotherapy+Cemiplimab | ACTIVE_COMPARATOR | Control treatment |
| Arm 1: Chemotherapy+Cemiplimab+REGN7075 | EXPERIMENTAL | Investigational Treatment |
| Phase 2: Cemiplimab | EXPERIMENTAL | Arm A: Cemiplimab is administered by IV infusion Q3W |
| Phase 2: BNT116 + Cemiplimab | EXPERIMENTAL | Arm B: BNT116 is administered by IV injection. Cemiplimab is administered by IV infusion Q3W. |
| Cemiplimab+ISA101b | EXPERIMENTAL | - |
| Melanoma intratumoral | EXPERIMENTAL | (CLOSED): Melanoma, IT VV1 + IV cemiplimab Patients will receive both treatments on Day 1 and every 3 weeks thereafter until lack of clinical benefit or limiting toxicity. VV1 or cemiplimab can continue after the first dose in combination or as a single agent treatment in subsequent doses. |
| Head and Neck SCC intratumoral | EXPERIMENTAL | HNSCC, IT VV1 + IV cemiplimab, Patients will receive both treatments on Day 1 and every 3 weeks thereafter until lack of clinical benefit or limiting toxicity. VV1 or cemiplimab can continue after the first dose in combination or as a single agent treatment in subsequent doses. |
| Colo-rectal Carcinoma intratumoral (Arm closed) | EXPERIMENTAL | (CLOSED) IT VV1 + IV cemiplimab, Patients will receive both treatments on Day 1 and every 3 weeks thereafter until lack of clinical benefit or limiting toxicity. VV1 or cemiplimab can continue after the first dose in combination or as a single agent treatment in subsequent doses. |
| Cohort A1 | EXPERIMENTAL | Cemiplimab prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual |
| Cohort A2 | EXPERIMENTAL | Cemiplimab and platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual |
| Cohort A3 | EXPERIMENTAL | Platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual |
| Cohort B | EXPERIMENTAL | Cemiplimab prior to surgery; cemiplimab post surgery (HCC) |
| Cohort C | EXPERIMENTAL | Cemiplimab prior to surgery; standard of care radiation and/or chemotherapy followed by cemiplimab post surgery (HNSCC) Not open for accrual |
| Cohort B2 | EXPERIMENTAL | SBRT 8 Gy X 3 fractions followed by cemiplimab prior to surgery; cemiplimab post surgery (HCC) |
| Cohort B3 | EXPERIMENTAL | Cemiplimab and fianlimab before and after surgery (HCC) |
| Group 1- metastatic BCC | EXPERIMENTAL | Administration of cemiplimab in accordance with protocol dosing regimen |
| Group 2 - unresectable locally advanced BCC | EXPERIMENTAL | Administration of cemiplimab in accordance with protocol dosing regimen |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg Q2W | EXPERIMENTAL | Participants received cemiplimab 3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks (Q2W) during each 8-week treatment cycle, for up to 96 weeks (12 cycles). |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg Q2W | EXPERIMENTAL | Participants received cemiplimab 3 mg/kg IV Q2W during each 8-week treatment cycle, for up to 96 weeks (12 cycles). |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg Q3W | EXPERIMENTAL | Participants received cemiplimab 350 mg IV every 3 weeks (Q3W) during each 9-week treatment cycle, for up to 54 weeks (6 cycles). |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg Q4W | EXPERIMENTAL | Participants received cemiplimab 600 mg IV every 4 weeks (Q4W) during each 8-week treatment cycle, for up to 48 weeks (6 cycles). |
| Group 5 (Participants With mCSCC and laCSCC): Cemiplimab SC + 350 mg Q3W | EXPERIMENTAL | Participants received a single subcutaneous (SC) dose of cemiplimab followed by cemiplimab 350 mg IV Q3W during each 9-week treatment cycle, for up to 54 weeks (6 cycles). |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg Q3W | EXPERIMENTAL | Participants received cemiplimab 350 mg IV Q3W during each 9-week treatment cycle, for up to 108 weeks (12 cycles). |
| Arm 1 Treatment with cemiplimab | EXPERIMENTAL | 350 mg cemiplimab intravenous (IV) every 3 weeks |
| Arm 2 Treatment with | EXPERIMENTAL | 350 mg cemiplimab intravenous (IV) + 1600 mg fianlimab intravenous (IV) every 3 weeks |
| Cohort 1: cemiplimab neoadjuvant treatment | ACTIVE_COMPARATOR | Patients will be treated with single agent intravenous cemiplimab 350 mg every 3 weeks for a total of 4 neoadjuvant cycles (12 weeks). |
| Cohort 2: cemiplimab plus topical imiquimod (plus fractional laser therapy) as neoadjuvant | EXPERIMENTAL | Patients will be treated with intravenous cemiplimab 350 mg every 3 weeks in combination with topical imiquimod 5% cream self-applied once daily 5 days per week (plus low-intensity laser therapy at 1- or 3-week interval), for a total of 4 neoadjuvant cycles (12 weeks). |
| Cohort A | EXPERIMENTAL | * 3 cycles of Cemiplimab-TP induction chemotherapy will be delivered in cohort A. * Cemiplimab-TP chemotherapy will be given every 21 days starting on days 1, 22 and 43, etc. (+ 2 days) with TP given on days 1, 22, and 43 (+/- 2 days) and Cemiplimab given on days 14, 35, 56 (+/- 2 days). * Patients in cohort A will get 3 doses of Cemiplimab during induction therapy. |
| ASP8374 and Cemiplimab-Cohort 1 | EXPERIMENTAL | A 3+3 dose escalation design will be used to determine maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ASP8374 when combined with cemiplimab. Participants will receive ASP8374 and Cemiplimab every 3 weeks for up to 2 years. ASP8374 will be available until October 31, 2022. Subjects may continue treatment with cemiplimab alone after that date. |
| ASP8374 and Cemiplimab-Cohort 2 | EXPERIMENTAL | Upon determination of the MTD/RP2D of ASP8374 plus cemiplimab in Cohort 1, a dose expansion will be performed in which eligible participants who are candidates for surgical resection will enroll to Cohort 2 and will be randomized into one of two treatment groups (2A-2B). Group 2A: IV ASP8374 plus cemiplimab within 14± 5 days prior to surgery at the MTD/RP2D established in Cohort 1. Group 2B: No immune checkpoint therapy prior to surgery. Post-operatively, all Cohort 2 participants will receive ASP8374 plus cemiplimab every 3 weeks administered at the MTD/RP2D established by Cohort 1 |
| Arm 1: Degarelix | ACTIVE_COMPARATOR | \- Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 |
| Arm 2: Degarelix and pTVG-AR | EXPERIMENTAL | * Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71 |
| Arm 3: Degarelix and pTVG-AR and Nivolumab | EXPERIMENTAL | * Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71 * Nivolumab 240 mg IV administered at days 29, 43, 57 and 71 |
| Arm 4: Degarelix and pTVG-AR and Cemiplimab | EXPERIMENTAL | * Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71 * Cemiplimab 350 mg IV administered at days 1, 22, 43 and 64 |
| Arm 5: Degarelix and pTVG-AR and Cemiplimab and Fianlimab | EXPERIMENTAL | * Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71 * Cemiplimab 350 mg IV administered at days 1, 22, 43 and 64 * Fianlimab 1600 mg IV administered at days 1, 22, 43 and 64 |
| Cohort 1 Cemiplimab | EXPERIMENTAL | Participants who received allogeneic hematopoietic stem cell transplant \-- Cemiplimab: via IV, flat predetermined dosage every 21 days |
| Cohort 2 Cemiplimab + Everolimus/Sirolimus + Prednisone | EXPERIMENTAL | Participants who received a kidney transplant will receive * Cemiplimab via IV, flat predetermined dosage every 21 days * Everolimus or Sirolimus-least 7-10 days prior to receiving the first dose of cemiplimab (Cycle 1, Day 1) and then daily while receiving Cemiplimab * Prednisone 40 mg orally the day prior to the start of cemiplimab dosing (Cycle 1, Day 1) and then daily at tapering doses while receiving Cemiplimab |
| Phase 1 Arm A | EXPERIMENTAL | Neoadjuvant Period: cemiplimab Adjuvant Period: fianlimab+cemiplimab |
| Phase 1 Arm B | EXPERIMENTAL | Neoadjuvant Period: fianlimab+cemiplimab Adjuvant Period: fianlimab+cemiplimab |
| Phase 2 | EXPERIMENTAL | Neoadjuvant Period: fianlimab+cemiplimab Adjuvant Period: fianlimab+cemiplimab |
| Dose Escalation | EXPERIMENTAL | 27T51 monotherapy |
| Dose Expansion - Arm A | EXPERIMENTAL | 27T51 monotherapy |
| Dose Expansion - Arm B | EXPERIMENTAL | 27T51+Cemiplimab |
| Dose Expansion - Arm C | EXPERIMENTAL | 27T51+Cemiplimab+Bevacizumab |
| Part 1, Dose escalation | EXPERIMENTAL | Pexa-Vec will be administered via IV infusion at a dose of 3 x 10\^8 pfu once per week for 4 treatments. Based on the occurrence of dose-limiting toxicities, patients may subsequently be enrolled to receive Pexa-Vec on the same schedule at a dose of 1 x 10\^9 pfu. Cemiplimab will be administered via IV infusion every 3 weeks. |
| Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab | EXPERIMENTAL | Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments. Cemiplimab will be administered via IV infusion every 3 weeks. |
| Part 2-Arm B, Cemiplimab | EXPERIMENTAL | Cemiplimab will be administered via IV infusion every 3 weeks. At disease progression, Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments. Cemiplimab will continue every 3 weeks. |
| Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab | EXPERIMENTAL | Pexa-Vec will be administered via IV infusion once per week for 4 treatments. Cemiplimab will be administered via IV infusion every 3 weeks. |
| Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab | EXPERIMENTAL | Pexa-Vec will be administered via IV infusion once per week for 4 treatments. Cemiplimab will be administered via IV infusion every 3 weeks. |
| REGN2810 | EXPERIMENTAL | REGN2810 administered IV over a 30 minute infusion |
| Cohort D | EXPERIMENTAL | Part 2 |
| Cohort E | EXPERIMENTAL | Part 2 |
| Dose escalation phase | EXPERIMENTAL | Safety assessment of odronextamab in combination with cemiplimab and selection of recommended phase 2 dose (RP2D) regimen(s) for the combination of odronextamab and cemiplimab. |
| Dose expansion phase | EXPERIMENTAL | RP2D administration of the combination treatment. |
| Monotherapy Cohort | EXPERIMENTAL | Cemiplimab will be administered alone |
| Dual Combination Cohorts | EXPERIMENTAL | Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy Doses of cemiplimab will be administered in combination with Cyclophosphamide Doses of cemiplimab will be administered in combination with Docetaxel |
| Triple Combination Cohorts | EXPERIMENTAL | Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus Cyclophosphamide Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF Doses of cemiplimab will be administered in combination with Carboplatin plus Paclitaxel Doses of cemiplimab will be administered in combination with Carboplatin plus Pemetrexed Doses of cemiplimab will be administered in combination with Carboplatin plus Docetaxel |
| Quadruple Combination Cohorts | EXPERIMENTAL | Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF plus Cyclophosphamide |
| Name | Type | Description |
|---|---|---|
| Cemiplimab | DRUG | Administered per protocol |
| Standard of care | PROCEDURE | Primary surgery |
| Placebo | DRUG | Intravenous (IV) infusion over 30 minutes |
| REGN2810 | DRUG | REGN2810 plus Platinum-based doublet chemotherapy Part 1 and Part 2 |
| REGN2810/chemo/ipi | DRUG | REGN2810 plus abbreviated chemotherapy plus Ipilimumab Part 1 |
| Chemotherapy | OTHER | Platinum-based doublet chemotherapy Part 1 |
| Investigator Choice (IC) Chemotherapy | DRUG | IC chemotherapy options include: 1. Antifolate: Pemetrexed 2. Topoisomerase 1 inhibitor: Topotecan or Irinotecan 3. Nucleoside analogue: Gemcitabine 4. Vinca alkaloid: Vinorelbine The only chemotherapy treatments allowed in the control arm are any of the 5 drugs that are listed as IC options above. |
| Pemetrexed | DRUG | Patients will be administered pemetrexed chemotherapy as per protocol with either cisplatin or carboplatin |
| Paclitaxel | DRUG | Patients will be administered paclitaxel chemotherapy as per protocol with either cisplatin or carboplatin |
| Gemcitabine | DRUG | Patients will be administered gemcitabine chemotherapy as per protocol with either cisplatin or carboplatin |
| Cisplatin | DRUG | Administered with either Pemetrexed, Paclitaxel or gemcitabine. |
| Carboplatin | DRUG | Administered with either Pemetrexed, Paclitaxel or gemcitabine. |
| Cemiplimab + Fianlimab [Fixed Dose Combination (FDC)] | DRUG | Immune checkpoint inhibition with antibodies directed against PD-1 and CTLA-4 receptors have demonstrated significant and durable efficacy in several advanced malignancies. LAG-3 is classified as an immune checkpoint protein that negatively regulates T cell activity, similar to PD-1 and CTLA-4. Blockade of LAG-3 with antibodies such as fianlimab, especially in combination with anti-PD-1 therapy, may represent a potentially effective or enhanced treatment for advanced malignancies. We hypothesize that cemiplimab in combination with fianlimab is feasible, safe, and effective neoadjuvant treatment strategy for early-stage colon cancer. |
| Cemiplimab Plus Gemcitabine | DRUG | Cemiplimab Plus Gemcitabine |
| Cemiplimab-Rwlc | DRUG | 350 mg every 3 weeks, intravenously, on day 1 of a 21 day cycle for 4 cycles, then every 3 weeks after surgery for 1 year. |
| Fianlimab | DRUG | 1600mg every 3 weeks for up to 24 months. |
| Pemetrexed (Alimta) | DRUG | 500 mg/m² every 3 weeks for 6 cycles. |
| Carboplatin (AUC 5) | DRUG | AUC 5 (recommended maximum dose of 800 mg) every 3 weeks for 6 cycles. |
| Cemiplimab 350 MG Intravenous Solution | DRUG | Cemiplimab is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells and was invented using Regeneron's proprietary Veloc Immune® technology. By binding to PD-1, cemiplimab (Libtayo) has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation. |
| Fianlimab 1600 MG Intravenous Solution | DRUG | Fianlimab is a recombinant fully human monoclonal antibody (based on IgG4 isotype) targeting the immune checkpoint receptor LAG-3 on T cells and was invented using Regeneron's proprietary Veloc Immune® technology. |
| Computed Tomography | PROCEDURE | Undergo CT scan |
| Biospecimen Collection | PROCEDURE | Undergo collection of blood samples |
| Quality-of-Life Assessment | OTHER | Ancillary studies |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI |
| Biopsy | PROCEDURE | Undergo biopsy |
| Motixafortide | DRUG | 1.25 mg/kg subcutaneous (SC) monotherapy daily for 5 days during priming, followed by twice weekly |
| Nab paclitaxel | DRUG | 125 mg/m2 IV on days 1, 8, 14 (every 28 days) |
| Degarelix | DRUG | Degarelix is administered subcutaneously (SC) at a dose of 240mg once. |
| Leuprolide Acetate | DRUG | Leuprolide acetate is provided at a dose of 22.5mg SC every 3 months. |
| Docetaxel | DRUG | Docetaxel is administered starting at week 10 at a dose of 75 mg/m2 every 21 days for up to 6 cycles. |
| Cemiplimab 350 mg IV | DRUG | three cycles of 350 milligrams of cemiplimab intravenously every three weeks |
| Vidutolimod | DRUG | Administered per the protocol |
| Prednisone | DRUG | Prednisone is administered orally and taken about the same time each day. Prednisone will be pulsed for Cycles 1-6 and continued to be pulsed or dose reduced for Cycles 7+. For Cycles 1-6: 40 mg dose will be administered the day before each cycle (Day -1 or Day 21) and Days 1-3, 20mg dose Days 4-6, and 10mg dose Days 7-20. For Cycles 7+: Dose will be administered pulsed as Cycles 1-6 or 10mg daily |
| Sirolimus | DRUG | Sirolimus will be taken orally once daily at dose prescribed to achieve a goal trough level of 4-6 ng/mL. It should be taken around the same time daily. Sirolimus will be administered daily throughout each cycle. |
| Cetuximab (EGFR inhibitor) | DRUG | Cetuximab may be administered according to standard of care (SOC). |
| NeuroBlate® Laser Ablation Laser Interstitial Thermal Therapy | DEVICE | LiTT, or magnetic resource imaging (MRI)-guided laser ablation, is a minimally invasive surgery approved for cytoreductive treatment of brain tumors. It employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MRI imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. |
| MaaT033 capsule | DRUG | MaaT033 capsule will be taken orally once a day for a week before every Cemiplimab cycle for the first 6 months of treatment. |
| Carboplatine | DRUG | Area Under the Curve (AUC) 5-6 at d1 q21 |
| Bevacizumab | DRUG | 10mg/kg at d1 and day 15 (d15) every 28 days (q28) |
| Vinorelbine i.v. 25 mg/m² | DRUG | 25-30 mg/m2 d1, d8 q21 |
| Vinorelbine oral | DRUG | 30 mg/50 mg per os 3 days per week (metronomic) |
| Encorafenib + Binimetinib | DRUG | Induction treatment with oral encorafenib 450 mg once daily (QD) + binimetinib 45 mg twice daily (BID)(combination: EB) for approximately two months (i.e. 8 weeks) |
| cemiplimab+fianlimab | DRUG | cemiplimab 350 mg + fianlimab 1600 mg combination every 3 weeks (Q3W)(Combination: CF) administered to patients intravenously (IV) for up to two years. |
| Platinum-based chemotherapy | DRUG | IV infusion |
| REGN7075 | DRUG | IV infusion |
| Fixed Dose Combination (FDC) cemiplimab+fianlimab | DRUG | Or coadministration, depending on availability. |
| BNT116 | DRUG | BNT116 is administered by IV injection. |
| ISA101b | BIOLOGICAL | Administered by subcutaneous (SC) injection on day 1, day 29, and day 50 |
| VV1 | BIOLOGICAL | VV1 is to be administered on Day 1 and every 3 weeks as long as there is clinical benefit |
| Platinum Doublet | DRUG | Administered intravenous (IV) |
| Arm 1 cemiplimab | DRUG | Cemiplimab 350mg IV every 3 weeks up to 1 year. |
| Arm 2 cemiplimab and fianlimab | DRUG | Cemiplimab 350mg IV and fianlimab 1600mg every 3 weeks up to 1 year |
| Topical imiquimod | DRUG | Topical imiquimod 5% cream self-applied once daily 5 days per week (plus low-intensity laser therapy at 1- or 3-week interval), |
| ASP8374 | DRUG | every 3 weeks by intravenous infusion |
| pTVG-AR | BIOLOGICAL | DNA vaccine encoding androgen receptor ligand-binding domain |
| Nivolumab | DRUG | Nivolumab is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with multiple different types of cancer. |
| FLT PET/CT | DRUG | Arms 1-3 only, FLT PET/CT scan at baseline (within 1-6 days of Day 1) and Day 43 |
| Everolimus | DRUG | Everolimus at least 7-10 days prior to receiving the first dose of cemiplimab (Cycle 1, Day 1) and then daily while receiving Cemiplimab |
| Cemiplimab+Fianlimab Fixed Dose Combination (FDC) | DRUG | Administered per the protocol |
| 27T51 | OTHER | Intravenous (IV) infusion |
| Pexastimogene Devacirepvec (Pexa-Vec) | BIOLOGICAL | Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells |
| Ipilimumab | DRUG | To be administered per protocol |
| Platinum-doublet chemotherapy | DRUG | To be administered per protocol |
| odronextamab | DRUG | Administration IV infusion. The dose(s) received will be according to DL cohort assignment, as described in the protocol. |
| Hypofractionated radiotherapy | RADIATION | - |
| Cyclophosphamide | DRUG | - |
| GM-CSF | DRUG | - |
Key Inclusion Criteria: 1. Participants who have a histologically confirmed invasive CSCC TL, as described in the protocol 2. Participants who have CSCC TL ≥1 cm and ≤2.0 cm (longest diameter) prior to biopsy and \>0.7 cm to ≤2.0 cm after biopsy, located in either the Head or Neck (HN), hand, or pr...
Cemiplimab is an investigational monoclonal antibody being developed by Regeneron Pharmaceuticals for the treatment of cancer. It is being studied in advanced cancer, advanced cutaneous squamous cell carcinoma, advanced non-small cell lung cancer, bladder cancer, and basal cell carcinoma. It is a PDCD1 inhibitor and is currently in Phase 1 development.
Cemiplimab targets PDCD1, also known as programmed cell death protein 1. It is a monoclonal antibody that acts as an inhibitor of this target. By binding PDCD1, cemiplimab is designed to interfere with a pathway that cancers use to suppress immune responses, allowing the immune system to attack tumor cells.
Cemiplimab is developed by Regeneron Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker REGN. Regeneron is the sponsor of the clinical trials evaluating cemiplimab across multiple cancer types, including cutaneous squamous cell carcinoma, non-small cell lung cancer, and basal cell carcinoma.
Cemiplimab is in Phase 1 development according to the current pipeline data. It is an investigational agent and is not described as approved. The clinical program includes five trials in total, with three active and three completed, and a combined enrollment of approximately 1,004 participants across the studies.
Cemiplimab is being studied in several trials, including NCT07808515 in locally advanced basal cell carcinoma, NCT07808138 in stage I non-small cell lung cancer in the Netherlands, NCT07746388 in resectable non-small cell lung cancer, and NCT07715734 in kidney transplant recipients with advanced cutaneous squamous cell carcinoma. All four listed trials are Phase 2 and not yet recruiting.
Yes, cemiplimab is also known as REGN2810. Other names used for this asset include cemiplimab-rwlc and cemiplimab 350 mg intravenous solution. Combination regimens under study are referred to as cemiplimab plus fianlimab, cemiplimab plus gemcitabine, and cemiplimab with fianlimab fixed dose combination.