Full Press Release Details
Initial Primary Analysis Results from CERPASS Clinical Trial in Advanced Cutaneous Squamous Cell Carcinoma and Presents New Data from
IGNYTE Clinical Trial of RP1 in Anti-PD1 Failed Melanoma and Non-Melanoma Skin Cancers
with cemiplimab demonstrated clinically meaningful improvements in complete response rate and duration of response compared to cemiplimab
in the CERPASS clinical trial, but did not meet either of the two primary endpoints
update for full 140 patients in the IGNYTE clinical trial cohort of RP1 in anti-PD1 failed melanoma reinforces durable benefit; biologics
license application (BLA) submission planned for 2H 2024
data from ARTACUS clinical trial and new data from first 30 patients with anti-PD1 failed non-melanoma skin cancers in IGNYTE trial adds
to growing body of evidence supporting the potential of RP1 in difficult to treat skin cancer settings
Portfolio reprioritization
extends cash runway to early 2026
conference call and webcast today at 8:00 am ET
WOBURN, Mass. December 5, 2023
- Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel portfolio
of oncolytic immunotherapies, today announced results from the primary analysis of the CERPASS trial evaluating RP1 in combination with
cemiplimab for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) and provided initial data for
all patients in the anti-PD1 failed melanoma cohort of the IGNYTE clinical trial. The company also shared a new data snapshot from the
IGNYTE cohort of anti-PD1 failed non-melanoma skin cancer (NMSC) patients and data from the ARTACUS trial evaluating RP1 as monotherapy
for skin cancer in patients who have had solid organ or hematopoietic cell transplants.
"Data from across our skin cancer
program clearly show that RP1 is an active agent both as monotherapy and in combination with anti-PD1 therapy in multiple settings, giving
us further confidence in the potential of RP1 to be an important treatment option for skin cancer patients," said Philip Astley-Sparke,
CEO of Replimune. "The overall data from the CERPASS study indicate that treatment with RP1 in combination with cemiplimab led
to clinically meaningful activity with a higher rate of complete responses and favorable duration of response versus cemiplimab alone.
Further, the positive data from the full 140 patient anti-PD1 failed melanoma cohort in the IGNYTE trial shows approximately 1 in 3 patients
treated with RP1 in combination with nivolumab achieved a durable response which we believe is supportive of our planned submission of
a BLA in 2H 2024 for this high unmet need patient population."
Results from the CERPASS Trial in
The CERPASS clinical trial was a
global, randomized study enrolling 211 patients randomized 2 to 1 to receive RP1 plus cemiplimab versus cemiplimab standard of care
for patients with locally advanced or metastatic CSCC. The CERPASS study was conducted under a Master Clinical Trial Collaboration
and Supply Agreement with Regeneron Pharmaceuticals.
The study did not meet either of the two primary endpoints of complete response
rate (CRR) or overall response rate (ORR) as assessed by blinded independent central review. RP1 in combination with cemiplimab
increased the CRR versus cemiplimab alone (38.1% vs. 25%, p=0.040), which was just short of the required threshold for statistical
significance in this study (p<0.025). Notably, among the 83 patients with locally advanced disease, the complete response
rate in the RP1 plus cemiplimab group was 48.1% versus 22.6% in the cemiplimab only group. The ORR was comparable between the two
study groups (52.5% for RP1 plus cemiplimab vs. 51.4% for cemiplimab alone, p=0.692). Importantly, RP1 in combination with
cemiplimab also increased duration of response (DOR) as compared to cemiplimab alone (hazard ratio 0.45), however, these data are
immature and further follow up is required. Of note, RP1 plus cemiplimab provided particularly meaningful clinical activity for many
patients with difficult to treat, disfiguring tumors that typically have the greatest impact on quality of life, given their size
There was also an imbalance in baseline
tumor burden across the treatment groups which may have impacted the number of responses seen. A significantly greater number of patients
with high baseline tumor burden (larger than 10 cm in total diameter) were treated in the RP1 plus cemiplimab group as compared to the
cemiplimab alone group (23% of RP1 plus cemiplimab treated patients had high baseline tumor burden vs. 12.5% of cemiplimab only patients).
In a pre-specified analysis, patients with total tumor burden less than or equal to 10 cm had a CRR of 43% in the RP1 plus cemiplimab
group versus 27% in the cemiplimab only group. For those patients with tumor burden greater than 10 cm, CRR was 21.9% in the RP1 plus
cemiplimab group versus 11.1% in the cemiplimab only group.
The trial will continue as planned to
assess DOR, progression free survival (PFS) and overall survival (OS) with greater maturity.
Treatment-related adverse events with
RP1 plus cemiplimab were predominantly additional transient Grade 1-2 "flu-like" symptoms being seen as compared to cemiplimab
alone, including fatigue, pyrexia, pruritis, nausea, hypothyroidism, chills, diarrhea, asthenia, infusion-related reaction, rash, rash
maculo-popular, and vomiting. There was a range of Grade 3 events occurring in one patient each in the RP1 plus cemiplimab arm (16.5%),
except for fatigue, rash maculo-popular, and immune-mediated hepatitis which occurred in 2 patients each. Grade 4 events were one each
of immune-mediated myocarditis and myocarditis. There were no Grade 5 treatment-related adverse events.
Initial Data from All Patients in
the IGNYTE Cohort of RP1 in Anti-PD1 Failed Melanoma
The registration directed anti-PD1 failed
melanoma cohort from the IGNYTE clinical trial includes 140 patients and completed enrollment earlier this year. Data are also included
for 16 patients from the initial cohort representing a total of 156 patients in this treatment setting.
In the RP1 plus nivolumab group (n=156),
the ORR was 31.4% with a CR rate of 12% showing activity consistent with the prior snapshot of 91 anti-PD1 failed melanoma patients.
As of this report, there are 5 patients still on study with the opportunity for response. In the full population, almost half of patients
failed combination therapy with ipilimumab plus nivolumab as compared to the earlier snapshot where approximately a third were ipilimumab
and nivolumab failures. Approximately 50% of patients experienced clinical benefit, defined as CR, PR, or stable disease (SD). Of responders,
100% are ongoing at more than six months with 78% of responses still ongoing as of November 6, 2023. Responses reported for this snapshot
were investigator-assessed. RP1 combined with nivolumab continues to be well-tolerated, with mainly Grade 1-2 "on target"
side effects, observed.
In this cohort, responses were seen
across disease stages, including complete responses in patients with stage IVM1b/c disease. Responses are highly durable with median
DOR greater than 24 months, and often deepening over time. Preliminary OS data are promising. The primary analysis by independent central
review will be triggered once all patients have had at least 12 months of follow up in March 2024.
Treatment-related adverse events associated
with RP1 in combination with nivolumab in this cohort were predominantly Grade 1-2 constitutional type events (> 5% of patients),
including fatigue, chills, pyrexia, nausea, influenza-like illness, pruritis, diarrhea, injection site pain, vomiting, headache, rash,
myalgia, asthenia, decreased appetite, and injection site reaction, with a low incidence of Grade 3-5 events. Grade 4 events were one
each of lipase increased, cytokine release syndrome, myocarditis and hepatic cytosis and the Grade 5 treatment-related adverse event
was one event of immune mediated myocarditis, which was attributed to nivolumab and is an expected immune mediated adverse event for
IGNYTE Regulatory Update
The company recently participated in
a Type C meeting with the U.S. Food and Drug Administration (FDA). During the discussion, the FDA acknowledged that the anti-PD1 failed
melanoma population is one of unmet need. The FDA agreed with an anti-PD1 failed melanoma confirmatory study design concept consisting
of a 2-arm randomized trial with physician's choice of treatment as a comparator arm in the study population. Full protocol development
is currently underway. The proposed Phase 3 confirmatory trial should be initiated by the time of an application under the accelerated
approval pathway. After following all patients for at least 12 months and pending central review by RECIST
v1.1, BLA submission for RP1 in combination with nivolumab is planned for 2H 2022.
Data Overview from Phase 1/2 ARTACUS
Clinical Trial of RP1 Monotherapy
As previously presented, treatment with
RP1 monotherapy in the Phase 1/2 ARTACUS clinical trial in skin cancer patients who have had solid organ or hematopoietic cell transplants
led to an ORR of 34.8% (8 of 23 evaluable patients, including 5 CRs and 3 partial responses). These patients are generally not eligible
for anti-PD1 therapy which could precipitate transplant rejection. Most responses were ongoing as of the data cutoff date of September
18, 2023. There was no evidence of allograft rejection. RP1 monotherapy was well tolerated, and the safety profile was similar to that
observed in non-immunocompromised patients with advanced skin cancers.
Initial Data Snapshot from the IGNYTE
Cohort of RP1 in Anti-PD1 Failed NMSC
The NMSC data reported from the IGNYTE
trial is from the first 30 patients enrolled in the cohort, all with at least 6 months of follow up, including patients with CSCC, MCC,
basal cell carcinoma, and angiosarcoma. The data show that treatment with RP1 in combination with nivolumab led to an ORR of 30% (9 of
30 patients) which is consistent with data from the anti-PD1 failed melanoma cohort with approximately a third of patients responding