pacmilimab (CX-072) / CytomX - LARVOL DELTA

CTMX-2009-002: Study to Evaluate the Safety and Antitumor Activity of CX-2009 Monotherapy and in Combination With CX-072 in Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=125 | Completed | Sponsor: CytomX Therapeutics | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Monotherapy • Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

The first-in-human, dose-finding PROCLAIM-CX-072 trial to assess the antitumor activity and tolerability of the probody therapeutic CX-072 as monotherapy and in combination with ipilimumab or vemurafenib in solid advanced tumors and lymphomas (ESMO 2017) - P1/2; "Efficacy will be determined according to irRECIST v1.1 criteria, and safety and tolerability will be assessed based on the incidence and nature of dose-limiting toxicities, adverse events (AEs), and serious AEs. Exploratory biomarkers will be used to characterize tumor protease activity, immune response pattern within the tumor, and CX-072 activation in tumor vs peripheral blood."

Checkpoint inhibition • Combination therapy • Monotherapy • Lymphoma • Melanoma

[VIRTUAL] A Phase 2, open-label study to evaluate the safety and efficacy of the probody therapeutic (Pb-Tx) CX‑2009 in metastatic HR-Positive/HER2-negative breast cancer (mHR+/HER2− BC) and of CX-2009 as monotherapy and in combination therapy with CX-072 in metastatic triple-negative breast cancer (TNBC) (SABCS 2020) - "This trial is actively enrolling. Email address for questions or comments: gpaton@cytomx.com"

Clinical • Combination therapy • IO Biomarker • Monotherapy • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Preliminary results of the first-in-human, dose-finding PROCLAIM-CX-072 trial evaluating the PD-L1 Probody therapeutic CX-072 in combination with ipilimumab (ipi) in patients (pts) with advanced solid tumors (ESMO 2018) - P1/2; "Despite small pt numbers and limited follow up, early data suggest manageable safety profiles at all doses and antitumor activity with CX-072 + ipi in tumor types not approved for checkpoint inhibitors. The study is ongoing and escalation of ipi to 10 mg/kg is pending."

Clinical • Combination therapy • P1 data • Solid Tumor

Preliminary results of PROCLAIM-CX-072: The first-in-human, dose-finding trial of PD-L1 Probody therapeutic CX-072 as monotherapy in patients (pts) with advanced solid tumors (ESMO 2018) - P1/2; "Preliminary data suggest that CX-072 demonstrates the characteristics of an antibody prodrug with antitumor activity and an acceptable safety profile in heavily pretreated pts with IMT-naive solid tumors. These data warrant further exploration of CX-072 as monotherapy and in combination with other anti-cancer agents."

Clinical • Monotherapy • P1 data • Breast Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • Thoracic Cancer • Thymus Cancer • Triple Negative Breast Cancer

CX-072, a PD-L1 Probody therapeutic, as monotherapy in patients with advanced solid tumors: Preliminary results of PROCLAIM-CX-072. (ASCO 2019) - P1/2; "CX-072 10 mg/kg monotherapy demonstrated anticancer activity in heavily pretreated pts with advanced solid tumors, including responses in cSCC, TNBC with skin lesions, and UPS, with a safety profile that compares favorably to historical controls. Clinical trial information: NCT03013491*Required postbaseline assessment."

Clinical • IO Biomarker • Monotherapy • PD(L)-1 Biomarker

Preliminary results of the first-in-human, dose-finding PROCLAIM-CX-072 trial of the PD-L1 Probody therapeutic CX-072 as monotherapy in patients (pts) with advanced solid tumors. (ASCO 2018) - P1/2; "Preliminary data for CX-072 in heavily pretreated pts with IMT-naive solid tumors where checkpoint blockade is unavailable as SOC for their disease show a manageable safety profile with signals of antitumor activity. These data warrant further exploration of CX-072 as monotherapy and in combination with other checkpoint inhibitors or targeted therapies."

Clinical • Monotherapy • P1 data • Neuroendocrine Tumor • Triple Negative Breast Cancer

Preliminary results from a phase 2 study of praluzatamab ravtansine (CX-2009) in patients with advanced breast cancer (ABC) (SABCS 2022) - P2 | "This phase 2 study (NCT04596150) evaluates CX-2009 as monotherapy in patients with advanced HR+/HER2− BC (Arm A) and TNBC (Arm B), and in combination with pacmilimab (a conditionally activated PD-L1) in TNBC (Arm C). Praluzatamab ravtansine demonstrated single-agent activity in unselected heavily pretreated patients with HR+/HER2- ABC. Time to event analyses, such as PFS, were confounded by higher-than-expected toxicity at a starting dose of 7 mg/kg. The toxicity profile was generally consistent with a DM4 payload."

Clinical • IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

CTMX-2009-002: Study to Evaluate the Safety and Antitumor Activity of CX-2009 Monotherapy and in Combination With CX-072 in Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=125 | Active, not recruiting | Sponsor: CytomX Therapeutics | Trial completion date: Sep 2023 ➔ Apr 2023 | Trial primary completion date: Sep 2023 ➔ Apr 2023

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

PROCLAIM-001: A first-in-human trial to assess tolerability of the protease-activatable anti-PD-L1 Probody CX-072 in solid tumors and lymphomas. (ASCO 2017) - P1/2; "...Ipilimumab (Parts B1 and B2) is dosed at the approved 3 mg/kg every 3 weeks x 4. The dose of vemurafenib (Part C) is 960 mg/kg twice daily. Exploratory biomarkers are used to characterize tumor protease activity, inflammatory changes within the tumor, and CX-072 activation in tumor versus peripheral blood."

Checkpoint inhibition • Biosimilar • Immunology • Lymphoma • Melanoma

Trial in progress: Phase 2, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine in metastatic HER2 non-amplified breast cancer as monotherapy and combination with pacmilimab (SABCS 2021) - P2 | "This study will also evaluate safety and tolerability, pharmacokinetics, and antidrug antibodies with praluzatamab ravtansine as monotherapy and in combination with pacmilimab. This trial is enrolling (NCT04596150)."

Clinical • Monotherapy • P2 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

CTMX-2009-002: Study to Evaluate the Safety and Antitumor Activity of CX-2009 Monotherapy and in Combination With CX-072 in Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=125 | Active, not recruiting | Sponsor: CytomX Therapeutics | Recruiting ➔ Active, not recruiting | N=200 ➔ 125

Combination therapy • Enrollment change • Enrollment closed • Monotherapy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

CytomX down 10% on CX-072 data (SeekingAlpha) - P1/2, N=14; PROCLAIM-CX-072 (NCT03013491); Sponsor: CytomX Therapeutics; "CytomX Therapeutics (CTMX -9.7%) slips on below-average volume in early trade following its announcement of results from a Phase 1/2 clinical trial, PROCLAIM-072, evaluating lead candidate CX-072, alone or in combination with Bristol-Myers Squibb's Yervoy (ipilimumab) or Roche's Zelboraf (vemurafenib), in patients with advanced unresectable solid tumors...In 14 evaluable patients who received CX-072 + Yervoy, the ORR was 21% (n=3/14) with a DCR of 43% (n=6/14)."

P1/2 data • Stock price • Oncology

CX-072 (pacmilimab), a Probody PD-L1 inhibitor, in advanced or recurrent solid tumors (PROCLAIM-CX-072): an open-label dose-finding and first-in-human study. (PubMed, J Immunother Cancer) - P1/2 | "Pacmilimab can be administered safely at the RP2D of 10 mg/kg every 14 days. At this dose, pacmilimab had a low rate of immune-mediated toxicity and showed signs of antitumor activity in patients not selected for high PD-L1 expression."

Clinical • IO biomarker • Journal • P1 data • Anal Carcinoma • Breast Cancer • Cardiovascular • Endocrine Cancer • Gastrointestinal Cancer • Inflammation • Oncology • Sarcoma • Small Intestinal Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Thymus Cancer • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • Undifferentiated Pleomorphic Sarcoma • CTLA4 • PD-L1 • TMB

CTMX-2009-002: Study to Evaluate the Safety and Antitumor Activity of CX-2009 Monotherapy and in Combination With CX-072 in Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: CytomX Therapeutics | N=150 ➔ 200 | Trial completion date: Mar 2023 ➔ Sep 2023 | Trial primary completion date: Mar 2023 ➔ Sep 2023

Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

CytomX Therapeutics to Present Updated Preclinical Data for Conditionally Activated Cytokine Program at AACR Annual Meeting 2022 (GlobeNewswire) - "'At the upcoming AACR Annual Meeting, we will report encouraging preclinical data that support the development of our conditionally activated interferon alpha-2b therapeutic candidate as a promising addition to current immunotherapy regimens, potentially expanding benefit to patients with typically unresponsive tumors.'"

Preclinical • Breast Cancer • Hematological Malignancies • Oncology • Solid Tumor • Triple Negative Breast Cancer

PROCLAIM-072 : PROCLAIM-CX-072: A Trial to Find Safe and Active Doses of an Investigational Drug CX-072 for Patients With Solid Tumors or Lymphomas (clinicaltrials.gov) - P1/2 | N=300 | Completed | Sponsor: CytomX Therapeutics | Active, not recruiting ➔ Completed | Trial primary completion date: Oct 2020 ➔ Oct 2021

Combination therapy • Monotherapy • Trial completion • Trial primary completion date • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Conditional PD-1/PD-L1 Probody therapeutics induce comparable antitumor immunity but reduced systemic toxicity compared with traditional anti-PD 1/PD-L1 agents. (PubMed, Cancer Immunol Res) - "Our results confirm that localized PD-1/PD-L1 inhibition by Pb-Tx can elicit robust antitumor immunity and minimize systemic immune-mediated toxicity. These data provide further preclinical rationale to support the ongoing development of the anti-PD-L1 Pb-Tx CX-072, which is currently in clinical trials."

Journal • Diabetes • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Obesity • Oncology

Preliminary single-dose clinical pharmacokinetics of an antiPD-L1 Probody therapeutic (Pb-Tx) in cancer patients. (ASCO 2018) - P1/2; " The phase 1-2 PROCLAIM-CX-072 (Probody Clinical Assessment In Man; NCT03013491) trial is a first-in-human study of CX-072 to characterize the safety, tolerability, pharmacokinetics (PK), and antitumor activity of CX-072 administered intravenously as a single agent or in combination with ipilimumab or vemurafenib in adult patients (pts) with cancer. Preliminary single-agent, single-dose CX-072 PK data suggest that CX-072 behaves as designed: it circulates predominantly as the intact prodrug species, and TMDD does not strongly influence its PK."

Clinical • PK/PD data • Oncology

Preliminary evidence of intratumoral activation and immunomodulatory effect of CX-072, a Probody therapeutic antibody prodrug targeting PD-L1, in a phase 1/2a trial (SITC 2018) - P1/2; "...Clinical pharmacokinetics and pharmacodynamics of atezolizumab in metastatic urothelial carcinoma...PROCLAIM-CX-072 is a first-in-human, phase 1/2, open-label dose-finding trial investigating the safety and maximum tolerated dose of CX-072 as monotherapy and in combination with ipilimumab or vemurafenib...Conclusions These preliminary results show the presence of relevant protease activity, intratumoral Probody therapeutic activation, and biological effect of a Probody therapeutic in human subjects treated with CX-072. Taken together with previous data demonstrating stability of the masked Probody therapeutic in systemic circulation [2], these results support proof-of-mechanism for the Probody platform."

IO biomarker • P1/2 data • PD(L)-1 Biomarker • Bladder Cancer • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Oncology • Urothelial Cancer

Preliminary interim results of the first-in-human, dose-finding PROCLAIM-CX-072 trial of the PD-L1 Probody therapeutic (Pb-Tx) CX-072 in combination with ipilimumab (ipi) in patients (pts) with advanced solid tumors. (ASCO 2018) - P1/2; "Preliminary data for CX-072 + ipi show a manageable safety profile and signals of antitumor activity. The study is ongoing, and all cohorts through 10 mg/kg CX-072, the dose selected for monotherapy cohort expansion, are now enrolled. Escalation of ipi dose to 10 mg/kg is pending."

Clinical • Combination therapy • IO biomarker • P1 data • PD(L)-1 Biomarker • Tumor Mutational Burden • Solid Tumor

[VIRTUAL] Evidence of intratumoral localization, activation, and immunomodulatory effect of CX-072, a probody therapeutic targeting PD-L1, in a phase I/II trial. (ASCO 2020) - P1/2 | "CX-072 is administered as monotherapy or in combination with ipilimumab to patients with metastatic or recurrent solid tumors or lymphomas for which approved PD-1/-L1–based therapy is not available. These results demonstrate that the Pb-Tx CX-072 behaves as designed in patients. Research Funding: CytomX Therapeutics, Inc."

IO biomarker • P1/2 data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Oncology • CD8

[VIRTUAL] PROCLAIM-CX-072: Analysis of patients with advanced solid tumors receiving long-term treatment with CX-072, a PD-L1 probody therapeutic, as a single agent or in combination with ipilimumab. (ASCO 2020) - P2 | "CX-072 monotherapy demonstrated durable responses consistent with activation of the PROBODY therapeutic in the TME. The safety profile supports the tolerability of CX-072 as monotherapy and when combined with IPI3. CX-072 + IPI3 demonstrated activity in heavily pretreated pts with various tumors."

Clinical • Combination therapy • Immune Modulation • Inflammation • Melanoma • Oncology • Solid Tumor • CTLA4

[VIRTUAL] CX-2009, a CD166-directed probody drug conjugate (PDC): Results from the first-in-human study in patients (Pts) with advanced cancer including breast cancer (BC). (ASCO 2020) - P1/2 | "Background: CX-2009 is a PROBODY drug conjugate (PDC) directed against CD166 (ALCAM) and conjugated to DM4, a potent microtubule inhibitor (MTI). CX-2009 at 7 mpk is the RP2D on Q3W schedule. Phase II expansion has begun in pts with HR+/HER2- BC. The Q2W schedule will continue to enroll pts to define the RP2D."

Clinical • IO Biomarker • P1 data • Breast Cancer • Fatigue • Gene Therapies • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immunology • Keratitis • Lung Cancer • Non Small Cell Lung Cancer • Ocular Inflammation • Oncology • Ophthalmology • Pain • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • HER-2

PROCLAIM-CX-072: Monotherapy for advanced triple negative breast cancer with skin metastases in a phase 1-2 trial of the PD-L1 probody therapeutic CX-072 (SABCS 2018) - P1/2; "Safety and tolerability will be assessed based on the incidence and severity of adverse events (categorized by NCI CTCAE criteria, v4.03) and relationship to study drug. Other analyses will include pharmacokinetics, incidence of anti-drug antibodies against CX-072, exploratory analysis for immune response, and CX-072 activation in the tumor.PROBODY is a trademark of CytomX Therapeutics, Inc. "

IO biomarker • Monotherapy • P1/2 data • PD(L)-1 Biomarker • Tumor Mutational Burden • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer