About

Robert G. Maki, MD, PhD, is an Adjunct Professor of Medicine in the Hematology-Oncology department at the Perelman School of Medicine, University of Pennsylvania. He specializes in medical oncology with expertise in connective tissue tumors, including sarcomas of soft tissue and bone, as well as locally destructive but non-metastatic connective tissue tumors such as desmoid tumors and giant cell tumors. His clinical expertise encompasses the development and implementation of clinical trials, particularly in phase I therapeutics, and the management of various sarcoma subtypes including angiosarcoma, Ewing sarcoma, rhabdomyosarcoma, and others. Dr. Maki's research focuses on translational oncology with a particular interest in epigenetics, tumor microenvironment, and metabolism as they relate to connective tissue tumors. His work involves basic science investigations aimed at understanding tumor biology and improving therapeutic strategies. He has contributed to the field through numerous publications and is actively involved in clinical trial design and translational research to advance treatment options for patients with sarcomas and related connective tissue tumors.

Research topics

• Medicine
• Internal medicine
• Oncology
• Cancer research
• Surgery

Selected publications

• Multi-Omic Landscape of Gastrointestinal Stromal Tumors in a Real-World Patient Cohort of 1,427 Cases

  Clinical Cancer Research · 2026-04-30

  article

  PURPOSE: Gastrointestinal stromal tumor (GIST) is a genomically-driven neoplasm with a genetic profile that determines the clinical course of the disease. However, currently available molecular data is limited due to the rarity of the disease and does not fully capture GIST clinical and biological heterogeneity. EXPERIMENTAL DESIGN: To gain deeper insight into the molecular landscape of GIST, we performed a comprehensive multi-omic analysis (targeted panel, whole exome sequencing, whole transcriptomics) in a large real-world, multicenter cohort including 1,427 cases. Pathological review was undertaken in KIT/PDGFRA-wild type cases. Molecular findings were correlated with clinical data and insurance claims outcomes. RESULTS: There is a complex spectrum of multi-layered genetic events that converge in three GIST molecular subgroups: KIT-mutant, PDGFRA-mutant, and KIT/PDGFRA-wild-type. These alterations can only be captured using next-generation sequencing technologies, and are associated with clinical features, biological aggressiveness, and patient outcomes. Mutations in alternative genes, whether actionable or not, are seldom present and unlikely to contribute to tumor progression. By contrast, the cooperative effect of novel somatic copy number alterations may be required for GIST evolution and progression, in addition to the core set of events involved in the current cytogenetic model of tumorigenesis. CONCLUSIONS: This molecular landscape provides a broader molecular understanding of GIST and supports a widespread use of genetic profiling for patients' clinical management.

  PublisherDOI

• Abstract CT295: Phase I trial of CRD3874-SI, a systemically administered third generation allosteric STING agonist, in patients with advanced solid tumors

  Cancer Research · 2026-04-17

  article

  Abstract Introduction: Identifying novel approaches that harness and augment anti-tumor immune response is an important area of ongoing research and drug development. Based on their performance in pre-clinical models, orthosteric activators of the Stimulator of Interferon Genes (STING) have been investigated in human trials. The activation of STING by its ligand cGAMP leads to both IFN dependent innate immune signaling as well as IFN independent pharmacology associated with STING's proton transport activity that leads to autophagy and pyroptosis. CRD3874 is a first in class small molecule allosteric STING agonist that binds to an allosteric site within STING's proton channel and decouples the IFN and non-IFN consequences of STING activation by blocking STING's non-IFN actions. CRD3874-SI, is a proprietary intravenous formulation of CRD3874, potent activator of all five human STING variants that has demonstrated promising pre-clinical anti-cancer activity in serval mouse tumor models when systemically administered as mono therapy or in combination with checkpoint therapy. Drug administration led to elevated plasma levels of CXCL10 and IFNβ in mice and monkeys. High IV doses up to 75mg/kg were systemically tolerated in cynomolgus monkeys. Methods: This is a single institution, phase Ia/b study of CRD3874-SI in patients with advanced solid tumors who received at least one line of prior therapy. The dose escalation phase will explore the safety and tolerability of CRD3874-SI following standard 3+3 design. CRD3874-SI is administered by intravenous infusion once per week for two cycles. From cycle 3 onwards, participants will received 3 or 4 consecutive weekly infusions, over a 28-day treatment cycle. The primary objective is to assess the safety and tolerability of CRD3874-SI by determining the maximum tolerated dose, recommended phase 2 dose and schedule of administration. Secondary objectives include further defining the safety profile, examining the pharmacokinetics and pharmacodynamics (CXCL10 analysis) of CRD3874-SI and evaluating the efficacy of CRD3874-SI as determined by the best objective response rate and clinical benefit rate per RECIST v1.1. Treatment will continue until disease progression or unacceptable toxicity. This study is currently open to enrollment. 21 patients have received treatment across 4 dose levels to date. Expansion cohorts are planned after determining the appropriate dose (RP2D). Clinical trial information: NCT 06021626. Research sponsor: Curadev Pharma, Inc. Citation Format: Ciara M. Kelly, Reinhard von Roemeling, Monali Banerjee, Viswatej Avutu, Olayade Babatunde, Lauren Banks, Ping Chi, Mark A. Dickson, Mrinal M. Gounder, Grace Gray, Camron Clark, Mary Louise Keohan, Robert G. Maki, Sujana Movva, Damon Reed, Kelly Schroeder, Li-Xuan Qin, Phillip Wong, Sandip Middya, Ritesh Shrivastava, Debjani Chakraborty, Rajib Ghosh, Sourav Basu, Arjun Surya, William D. Tap, Sandra P. D'Angelo. Phase I trial of CRD3874-SI, a systemically administered third generation allosteric STING agonist, in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT295.

  PublisherDOI

• Trabectedin and low-dose irinotecan to target EWS::FLI1 in Ewing sarcoma: a phase 1/2 trial

  Nature Medicine · 2026-04-16

  article
  PublisherDOI

• Phase 2 study of palbociclib plus retifanlimab in patients with advanced dedifferentiated liposarcoma

  Journal for ImmunoTherapy of Cancer · 2026-05-01

  articleOpen access

  Background The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib delays disease progression in dedifferentiated liposarcoma (DDLPS) by inducing tumor cell quiescence or senescence, though most tumors ultimately progress. Preclinical data suggest CDK4/6 inhibition enhances intratumoral inflammation and may synergize with immune checkpoint inhibitors. Methods This non-randomized, open-label, phase 2 study was conducted at Memorial Sloan Kettering Cancer Center. Patients with metastatic or unresectable DDLPS, or those expected to benefit from systemic therapy prior to surgery, were eligible. Patients received palbociclib (125 mg orally, days 1–21 of a 28-day cycle) plus retifanlimab (500 mg intravenous flat dose every 4 weeks). The primary endpoint was to assess the best objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results 30 patients were treated and evaluable. Median age was 61 years (range 36–81), 67% were male, and 63% were treatment-naive. The median follow-up was 14.8 months. ORR was 20% (95% CI 8% to 39%) and the clinical benefit rate was 53% (95% CI 34% to 72%). Median progression-free survival and overall survival were 4.8 (95% CI 1.71 to 15.7) and 27 months (95% CI 21.7 to not reached (NR)), respectively. Median duration of response was 18.4 months (95% CI 9.4 months to NR). Grade ≥3 treatment-related adverse events occurred in 61% of patients, including one Grade 4 neutropenia. There were no Grade 5 events. Retifanlimab and palbociclib were discontinued due to toxicity in 23% and 17% of patients, respectively. Tumor sequencing identified JUN amplification in 6 of 14 patients with progressive disease versus 2 patients with stable disease or partial response. Patients with progressive disease had a higher median copy number alteration burden compared with those with stable disease or partial response. Conclusions Palbociclib plus retifanlimab demonstrated deep and durable responses in a subset of patients with advanced DDLPS, with an ORR exceeding that historically observed with either agent alone. Adverse events were generally manageable. Copy number alteration burden and JUN amplification merit further evaluation as potential biomarkers of resistance. Trial registration number https://clinicaltrials.gov/study/NCT04438824 .

  PublisherDOI

• Systemic Therapy Outcomes for Soft Tissue Leiomyosarcoma Patients in an Era of Next-Generation Sequencing

  JCO oncology advances. · 2026-01-01

  articleOpen accessSenior author

  PURPOSE Next-generation sequencing (NGS) provides an opportunity to leverage genomic data to identify novel factors associated with treatment outcomes. We examined outcomes of systemic therapy in patients with soft tissue (nonuterine) leiomyosarcoma (LMS) who had NGS at our center to identify associations of those NGS findings with radiologic outcomes. METHODS We reviewed 168 patients with soft tissue LMS who received systemic therapy between 2009 and 2024 for metastatic LMS and also had Memorial Sloan-Kettering Integrated Mutation Profiling of Actionable Cancer Targets profiling. We conducted univariate and multivariate Cox regression analyses of clinicopathologic factors and genomic alterations for progression-free survival (PFS) for first- and second-line systemic therapy. RESULTS There were 110 female and 58 male patients in this cohort. Patients received 1-12 lines of systemic therapy for metastatic disease. Treatment regimens were categorized as (1) doxorubicin-based, (2) pegylated liposomal doxorubicin (PLD)–based, (3) gemcitabine-based, (4) pazopanib, and (5) other. On univariate analysis, inferior PFS for first-line chemotherapy was associated with high mitotic activity, necrosis, and TP53 or RB1 mutation. On multivariate analysis, only the therapeutic class was associated with PFS, with statistically inferior outcomes for PLD-containing combinations across the full cohort. Tumor size >10 cm, high mitotic rate, and TP53 alterations were associated with inferior PFS in the PLD-based treatment subgroup. High mitotic rate was associated with inferior PFS in the gemcitabine-based treatment subgroup. CONCLUSION Both doxorubicin- and gemcitabine-based therapy showed significantly greater activity than PLD-based therapy. NGS results were not predictive for outcomes with first- or second-line treatment for metastatic soft tissue LMS. These data may merit re-examination when data are accumulated regarding the increasing use of doxorubicin-trabectedin in this population.

  PublisherDOI

• Molecular Profiling for Precision Oncology: Moving Beyond Feasibility and Safety

  Journal of Clinical Oncology · 2026-01-14

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Real‐World Experience of Efficacy and Tolerability of Continuous Infusion Ifosfamide for Advanced Soft Tissue and Bone Sarcoma Patients: A Single Centre Retrospective Cohort

  Cancer Medicine · 2026-02-01

  articleOpen access

  BACKGROUND: In the absence of randomized trials, selecting second or later-line therapies in advanced sarcoma generally hinges on histology, patient performance status, and toxicity profile. We herein report a real-world sarcoma referral center experience on continuous infusion Ifosfamide (ciIFO), in advanced Soft tissue sarcomas (STS) and bone sarcomas (BS) patients, assessing both efficacy and toxicity profile. METHODS: as a 14-day continuous infusion every 4 weeks) at our Institute from January 2013 to April 2023. The analysis included patients' demographic and clinical characteristics, pathology details, treatment history, radiological response rates (RR), and toxicities per Common Terminology Criteria for Adverse Events (CTCAE) v5. RESULTS: Ninety eight patients were included in the analysis. Median age at diagnosis was 49 years, 61% had previously received ifosfamide (IFO) and 83% anthracycline in earlier lines of treatment. Disease control rate (DCR) was 32%, with 9 PR and 22 stable disease (SD). Synovial sarcomas had the best (DCR) (60%). No statistically significant differences in DCR were seen according to sex, previous exposure to ifosfamide-based CT, or ciIFO treatment line. mPFS was 3.0 months; mOS was 11.2 months. ciIFO was well tolerated, with an 11% discontinuation rate and no severe renal toxicity observed. CONCLUSIONS: ciIFO showed activity across different lines of therapy, achieving a DCR of 32%, and appeared better tolerated than standard-dose IFO regimens, even in a cohort of heavily pretreated patients (18% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2). Synovial and bone sarcoma patients derived the greatest benefit (6-month PFS of 45% in both groups).

  PublisherOA PDFDOI

• ctDNA as a Molecular Biomarker in the Phase II Trial of Imatinib plus Binimetinib in Patients with Advanced Gastrointestinal Stromal Tumor

  Clinical Cancer Research · 2025-07-22 · 1 citations

  article

  PURPOSE: This study investigated factors that affected ctDNA detection and ctDNA as a molecular biomarker in a phase II trial of imatinib and binimetinib in newly diagnosed advanced gastrointestinal stromal tumor, including patients exposed to imatinib within 4 weeks of trial enrollment. EXPERIMENTAL DESIGN: Plasma and tumor tissue samples were collected at baseline, during treatment, and upon progression. DNAs extracted from plasma and tumor tissue were analyzed using genomic assays, Memorial Sloan Kettering Analysis of Circulating cfDNA to Evaluate Somatic Status and Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets, respectively. Sequenced ctDNA detection of the primary oncogenic driver was determined and correlated with clinical characteristics. RESULTS: Patients (n = 31) included in this analysis had KIT mutations (n = 29, 94%) and metastatic disease (n = 24, 77%) and achieved the best response of partial response (n = 22, 71%), stable disease (n = 8, 26%), or progressive disease (n = 1, 3%). Sixteen patients (52%) were exposed to imatinib at baseline. The ctDNA detection rate of the primary oncogenic driver at baseline was 39% (n = 12/31) and was significantly more likely in patients who were treatment-naïve (n = 15) or had ≤4.2 weeks of treatment (n = 8) than in those otherwise (48% vs. 13%; P value = 0.004). Baseline ctDNA detection did not correlate with tumor burden or stage. The ctDNA serial analysis of the primary oncogenic driver paralleled and sometimes preceded radiographic response. ctDNA detected resistance mutations in KIT (n = 4). Active treatment influenced the detection of secondary KIT alterations in one patient. CONCLUSIONS: Active therapy at the time of ctDNA collection negatively affected the ability to detect primary and secondary KIT alterations in sequenced ctDNA from patients with advanced gastrointestinal stromal tumor. ctDNA responses may precede radiographic responses and merit further investigation.

  PublisherDOI

• Evaluation and Management of Sarcomas

  2025-05-01

  book-chapter1st authorCorresponding
  PublisherDOI

• Phase II study of rucaparib and nivolumab in patients with leiomyosarcoma

  Journal for ImmunoTherapy of Cancer · 2025-06-01 · 4 citations

  articleOpen access

  Background Objective responses to immune checkpoint inhibitors (ICI) in leiomyosarcoma (LMS) are rare. Response rates may be increased by combination with other drugs known to promote immune infiltration, such as poly(ADP-ribose) polymerase (PARP) inhibitors, which have led to benefit in BRCA -altered uterine LMS. We therefore evaluated the combination of a PARP inhibitor, rucaparib, and the anti-programmed death receptor-1 monoclonal antibody, nivolumab, in patients with advanced LMS and investigated its effects on the tumor immune microenvironment. Methods This was an open-label, single-center, single-arm, phase II study in patients with advanced refractory LMS. Full protocol available Patients were treated with rucaparib 600 mg orally, two times daily, continuously and nivolumab 480 mg intravenously on day 1 of a 28-day cycle. Re-staging scans were performed every 8 weeks. Blood and tissue samples were collected at baseline and at week 8 on treatment. The primary objective was the best objective response rate by 24 weeks using Response Evaluation Criteria in Solid Tumour (RECIST V.1.1). Secondary objectives included treatment-related toxicity, progression-free survival, overall survival, and changes in immune pathways in blood and tumor. Results 20 patients with LMS were enrolled. There was one partial response (PR) (5%) in a patient with uterine LMS and a somatic BRCA deep deletion. 19 (95%) patients had a treatment-related adverse event (TRAE) and 7 (35%) had a grade 3 or higher TRAE. Interferon (IFN) α and γ hallmark pathways were more highly expressed in patients who derived benefit from treatment (at least stable disease by 16 weeks) vs those who did not in both baseline (adjusted p=0.005 for IFN-α, 0.03 for IFN-γ) and on-treatment biopsies (adjusted p=0.0002 for IFN-α, 0.0001 for IFN-γ), but the abundance of tumor immune cell populations did not differ between these groups at either time point. Conclusion The addition of a PARP inhibitor did not improve the efficacy of ICI in LMS. Adverse events, especially due to overlapping toxicities, were frequent and often led to dose delays and modifications.

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Recent grants

• NIH Grant RC2CA148260

  NIH · $2.4M · 2012

Frequent coauthors

• William D. Tap

  595 shared

• Susan M. Chang

  Neurological Surgery

  538 shared

• Bryan J. Schneider

  Michigan Medicine

  529 shared

• Merry Jennifer Markham

  University of Florida

  529 shared

• Michael S. Sabel

  Heinrich Heine University Düsseldorf

  529 shared

• Randall J. Kimple

  529 shared

• Gabrielle B. Rocque

  University of Alabama at Birmingham

  529 shared

• Noelle K. LoConte

  University of Wisconsin Carbone Cancer Center

  529 shared

Education

• Fellow, Medical Oncology

  Dana Farber Cancer Institute

  1998

• Medical Intern, Resident, Medicine

  Brigham and Women's Hospital

  1995

• MD, N/A

  Cornell University Medical College

  1992

• PhD, Immunology

  Cornell University Graduate School of Medical Sciences

  1991

• BA, Integrated Science Program

  Northwestern University

  1985