About

Ravi K Amaravadi, MD, is the Tara Miller Professor of Melanoma Research and Patient Care at the University of Pennsylvania's Perelman School of Medicine. He is an attending physician at the Hospital of the University of Pennsylvania and a member of the Abramson Cancer Center, the Institute of Translational Medicine and Therapeutics, and the University of Pennsylvania GI Center for Molecular Studies of Digestive and Liver Diseases. His research expertise includes autophagy, mechanisms of cell death, and developmental therapeutics, with a clinical focus on Phase I and Phase II clinical trials in melanoma. Dr. Amaravadi's work involves understanding and targeting cellular processes to develop novel therapeutic strategies for melanoma and other cancers, contributing significantly to translational research in oncology.

Research topics

• Biology
• Cell biology
• Internal medicine
• Medicine
• Immunology
• Biochemistry
• Cancer research
• Chemistry
• Genetics
• Oncology
• Microbiology
• Computational biology
• Pathology
• Materials science
• Evolutionary biology

Selected publications

• Compliance with guidelines and timeliness of sentinel lymph node biopsy for Merkel cell carcinoma treated with Mohs micrographic surgery versus conventional excision at a tertiary academic center

  Journal of the American Academy of Dermatology · 2025-10-17

  article
  PublisherDOI

• Supplementary Data Figures S1-S5 from Targeting UGCG Overcomes Resistance to Lysosomal Autophagy Inhibition

  2025-12-11

  articleOpen accessSenior author

  <p>Supplemental Figure S1: LAI remodels the lipidome of melanoma cells. Supplemental Figure S2: LAI induces UGCG, and UGCG inhibition augments DC661 cytotoxicity, and this effect is not seen by blocking cholesterol synthesis and key earlier steps of autophagy. Supplemental Figure S3: LAI increases the formation of GMM in cancer cells. Supplemental Figure S4: UGCG inhibition synergistically augments LAI induced cytotoxicity and abrogates GMM formation without elevating ceramide levels. Supplemental Figure S5: LAI induces UGCG-associated GMM formation in PDX cells, a combination of DC661 and eliglustat impairs tumor growth in a therapy-resistant PDX tumor model.</p>

  PublisherOA PDFDOI

• Neoadjuvant-adjuvant pembrolizumab in clinical stage IIB/C melanoma.

  Journal of Clinical Oncology · 2025-05-28 · 7 citations

  article

  9502 Background: Neoadjuvant immune checkpoint therapy has shown improvement in event-free survival outcomes in patients with resectable clinical stage III and IV melanoma. Whether there is benefit to neoadjuvant immune therapy in patients with clinical stage IIB/C melanoma is unknown. Methods: In a single arm multicenter investigator-initiated phase 2 trial, patients with clinical stage IIB/C melanoma received a single dose of neoadjuvant pembrolizumab (200 mg intravenously) 3 weeks prior to wide excision and sentinel lymph node (SLN) biopsy followed by 1 year adjuvant pembrolizumab every 3 weeks or until unacceptable toxicity or disease progression. Primary endpoint was SLN positivity rate. A sample size of 63 patients had 80% power detect a 50% difference when compared to a predetermined historical SLN positivity rate in treatment naïve patients (25% Stage IIB and 40% Stage IIC) weighted by proportion of clinical tumor stage in eligible study patients. Secondary endpoint included recurrence-free survival. Safety outcomes, including overall toxicity and immune related adverse events, were also assessed. Results: Of 63 evaluable patients (33 IIB; 30 IIC at initial biopsy), the SLN metastasis rate in the neoadjuvant study group was 27%. 28 patients (44%) had residual primary tumor after single dose pembrolizumab; 4 patients had their primary tumors upstaged to IIC. Compared to a SLN metastasis rate in a historical treatment- naïve cohort based on tumor staging at wide excision (33.1%), there was a 18% reduction in SLN positivity rate in the neoadjuvant group, although this was not statistically significant (p = 0.302). In a subgroup analysis, stage IIC patients in the neoadjuvant study group had a SLN metastasis rate of 16.7% versus 40% (p = 0.009) based on initial biopsy and 23.5% versus 40% (p = 0.0499) based on primary tumor staging at wide excision. With median follow-up of 20.4 months, the 2-year recurrence free-survival in the study group was 84% with median time to recurrence (n = 10) of 9.9 months. Overall treatment-related grade 3/4 adverse events were 14 (22%) with 9 (14%) immune-related adverse events; there was no delay in definite surgery secondary to neoadjuvant treatment. Conclusions: Rate of SLN metastasis among patients with clinical stage IIB/C melanoma undergoing neoadjuvant pembrolizumab did not differ significantly compared to expected historical rates in treatment-naïve patients; however, in a secondary subgroup analysis among patients with clinical stage IIC disease, a decrease in SLN positivity rate was noted. Neoadjuvant therapy in clinical stage IIB/C was safe and feasible, with no significant delay in surgery or new or unexpected toxicities noted in these patients. Translational studies are under way, including flow cytometric and transcriptional studies, that may reveal immunologic determinants of efficacy versus resistance. Clinical trial information: NCT03757689 .

  PublisherDOI

• DR5 CAR-T cells target melanoma and suppress MDSCs with minimal toxicity

  Molecular Therapy · 2025-12-11

  articleOpen access
  PublisherOA PDFDOI

• The Landscape of Gain and Loss of Function Mutations in Melanoma

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Antigen-Specific Profiling Identifies T-bet-Expressing Melanoma-Specific CD8 T Cells Associated with Pathologic Response to Neoadjuvant Anti-PD-1

  SSRN Electronic Journal · 2025-01-01 · 1 citations

  preprintOpen access
  PublisherDOI

• RDTA-13 OUTCOMES AFTER SRS AND IPILIMUMAB/NIVOLUMAB FOR PATIENTS WITH MELANOMA BRAIN METASTASES WITH OR WITHOUT PRIOR CHECKPOINT EXPOSURE

  Neuro-Oncology Advances · 2025-08-01

  articleOpen access

  Abstract While ipilimumab/nivolumab has demonstrated promising intracranial activity among patients with melanoma brain metastases (BM), patients with prior immune checkpoint inhibition (ICI) exposure may be at higher risk of worse intracranial disease control. We evaluated outcomes of patients with melanoma BM treated with ipilimumab/nivolumab and stereotactic radiosurgery (SRS) with or without prior ICI. Overall survival (OS) and intracranial progression-free survival (iPFS) were estimated from SRS using a non-parametric method, and Cox proportional hazards models were used to test clinically relevant factors. 64 consecutive patients with 393 treated BM between 2015 and 2024 were included with median follow-up of 20.2 months from SRS. 34 (53%) patients were alive at analysis. The 2-year OS and iPFS for the entire cohort was 52.1% and 36.4%, respectively. 32 patients (50%) had prior exposure to ICI. Performance status, age, number of BM, and receipt of surgery were not significantly different among patients with or without prior ICI. Patients with prior ICI had smaller BM (largest median diameter 19 mm vs 22.5 mm, p=0.022) and were less likely to have extracranial metastases (53.1% vs 78.1%, p=0.035). Patients with prior ICI exposure trended towards worse iPFS (median iPFS 4.3 months vs 13.5 months, p = 0.29) and had worse survival after SRS (median OS 17.6 months vs 50.5 months, p = 0.017). On univariate analysis, receipt of prior ICI (HR 2.16, 95% CI 1.13 – 4.11, p = 0.019), no upfront surgery (HR 0.38, 95% CI 0.20 – 0.72, p = 0.003), and number of treated BM (HR 1.04, 95% CI 1 – 1.08, p = 0.043) were significantly associated with OS. While ipilimumab/nivolumab with SRS demonstrates encouraging intracranial control, patients with prior ICI exposure are at higher risk of poor outcomes and may benefit from additional treatment strategies.

  PublisherOA PDFDOI

• Single-Dose Neoadjuvant Pembrolizumab in Resectable Metastatic Melanoma

  Annals of Surgical Oncology · 2025-09-12 · 2 citations

  articleOpen access

  INTRODUCTION: Neoadjuvant immune checkpoint blockade therapy for resectable oligometastatic melanoma has shown promising results in clinical trials; however, investigation into the optimal agent and dosing schedule is ongoing. We report on the largest case series of patients with oligometastatic melanoma treated with a single dose of neoadjuvant programmed cell death receptor 1 (PD-1) inhibition. METHODS: We identified PD-1 naive patients with resectable stage III/IV melanoma who received one dose of pembrolizumab (200 mg intravenous) prior to surgical resection at a single high-volume melanoma center. Outcomes included time to surgery, 30-day surgical complications, time to initiation of adjuvant therapy, major pathologic response (MPR) defined as < 10% viable tumor, patterns/treatment of first recurrence, and 5-year recurrence-free and overall survival. RESULTS: Of 51 patients, there were no grade 3/4 immune-related adverse events prior to surgery and no delays in surgery. The majority of patients (70.6%) had no postoperative complications, and none were Clavien-Dindo grade 3 or higher. There was prompt initiation of adjuvant therapy, along with appreciable rates of MPR (19.6%). In total, 45.1% of the cohort experienced a recurrence including two patients who had an MPR. For patients who achieved MPR, 5-year overall survival was 100%. CONCLUSIONS: A single dose of neoadjuvant pembrolizumab is a safe and feasible approach with potential for early pathological readout of responsiveness to neoadjuvant therapy. Late recurrences were observed in the MPR group, indicating need for follow-up but were salvageable. Further biomarker work is needed to identify patients who would benefit from neoadjuvant single agent anti-PD-1 therapy.

  PublisherOA PDFDOI

• Taxonomy-free fecal microbiome profiles enable robust prediction of immunotherapy response and toxicity in melanoma

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-07

  preprintOpen access

  The gut microbiome has been causally linked to the efficacy of immune-checkpoint inhibitor therapy (ICI), prompting numerous clinical trials of microbiome-targeting strategies. Yet, mechanisms by which gut microbiota shape immune responses remain elusive as taxonomic biomarkers have failed to generalize across multiple cohorts. In this study, we develop a taxonomy-agnostic framework to identify microbial biomarkers of ICI response and immune-related adverse event (irAE) occurrence from metagenomic sequencing. Applying this approach to four independent melanoma cohorts from clinical centers across the United States, we uncover gut microbial proteins produced by diverse bacterial taxa that consistently predict ICI response. Notably, we uncover a previously uncharacterized operon involved in cellular redox homeostasis that is encoded by different bacteria and reliably predicts irAE occurrence. We further validated the predictive power of this operon in a prospectively sequenced melanoma cohort. Our results demonstrate that taxa-agnostic microbial protein biomarkers are robust, generalizable, and provide a path towards pretreatment risk stratification for melanoma patients initiating ICI therapy.

  PublisherDOI

• Combination ipilimumab/nivolumab for refractory Merkel cell carcinoma: A single-institution experience.

  Journal of Clinical Oncology · 2025-05-28 · 1 citations

  article

  e21528 Background: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor with an aggressive disease course. Many patients will recur or progress following resection and first-line systemic therapy, and salvage therapy options are limited. Recent studies evaluating combination ipilimumab/nivolumab (ipi-nivo) as second-line therapy for refractory/advanced MCC have found mixed results, and the standard-of-care for this patient population is not yet defined. Given the lack of consensus on ideal regimens for refractory disease, we report our institutional experience with combination ipi-nivo. Methods: In this retrospective analysis, we reviewed the electronic medical record at the Hospital of the University of Pennsylvania from 2015 – 2025 for patients with MCC who had progressive/recurrent disease following first-line therapy (surgery ± chemotherapy, radiation, and/or immunotherapy) who were treated with ipilimumab 3 mg/kg and nivolumab 1 mg/kg. Objective treatment responses to ipi-nivo were determined at regular intervals based on Response Evaluation Criteria in Solid Tumors Version 1.1. The primary outcome was objective response rate (ORR), and secondary outcomes were progression-free survival (PFS) and toxicity profile. Survival estimates were calculated using the Kaplan-Meier method. Results: A total of 17 patients met inclusion criteria, of which 13 (76%) were male; median age at initiation of ipi-nivo was 70 years (interquartile range [IQR] 66 – 74). Four (24%) patients achieved a complete response (CR) and 2 (12%) achieved partial response (PR), with an ORR of 36%. Two patients were immunotherapy-naïve prior to initiating ipi-nivo and of these, 1 patient had PR. Median duration of response (DOR) was 6.6 months (IQR 4 – 14). At the latest follow-up period, of the patients that had objective response to ipi-nivo, 1 patient died of other causes and 5 patients had sustained response. Median PFS was 2.8 months (95% confidence interval [CI]: 0.9 – NR) at median follow-up of 12 months. Estimated 1-year PFS was 34.3% (95% CI: 13 – 57) and 1-year overall survival (OS) was 63.3% (95% CI: 36 – 82). In the overall cohort, 8 (47%) patients were still alive at latest follow-up. Grade 3/4 immune-related adverse events (irAE) occurred in 3 (18%) patients, of which 2 patients had to permanently discontinue therapy. Conclusions: Our single-institution experience adds to the currently limited body of literature for refractory MCC, suggesting that ipi-nivo is a viable strategy with durable response rates and a tolerable toxicity profile. Outcomes for patients receiving ipi-nivo for refractory MCC (n = 17). ORR, n (%) 6 (36) CR, n (%) 4 (24) PR, n (%) 2 (12) SD, n (%) 2 (12) PD, n (%) 9 (53) Median DOR, m (IQR) 6.6 (4 – 14) Median PFS, m (95% CI) 2.8 (0.9 – NR) 1-year PFS, % (95% CI) 34.3 (13 – 57) 1-year OS, % (95% CI) 63.3 (36 – 82) Grade 3/4 irAE, n (%) 3 (18) SD – stable disease, PD – progressive disease, NR – not reached, m – months.

  PublisherDOI

Recent grants

• NIH Grant K23CA120862

  NIH · $686k · 2014

• Targeting HSP70 for MelanomaTherapy

  NIH · $69.3M · 2008–2025

• Molecular mechanisms of BRAF inhibitor induced UPR and autophagy

  NIH · $1.8M · 2015–2021

• Developmental Research Program

  NIH · $17.8M · 2021

• Radiobiology and Imaging Program

  NIH · $93.0M · 1997–2027

Frequent coauthors

• Lynn M. Schuchter

  University of Pennsylvania

  315 shared

• Giorgos C. Karakousis

  202 shared

• Tara C. Mitchell

  165 shared

• Meenhard Herlyn

  162 shared

• Qin Liu

  Nanjing Drum Tower Hospital

  138 shared

• Keith T. Flaherty

  Massachusetts General Hospital

  131 shared

• Xiaowei Xu

  The Wistar Institute

  120 shared

• Alexander C. Huang

  University of Pennsylvania

  101 shared

Labs

• Amaravadi LabPI

Awards & honors

• Tara Miller Professor of Melanoma Research and Patient Care
• Member, Abramson Cancer Center
• Member, Institute of Translational Medicine and Therapeutics
• Member, University of Pennsylvania GI Center for Molecular S…
• Co-Director, University of Pennsylvania/Wistar Institute SPO…