pacmilimab (CX-072) / CytomX - LARVOL DELTA

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=196 | Terminated | Sponsor: CytomX Therapeutics | N=300 ➔ 196 | Completed ➔ Terminated; Sponsor's decision

Enrollment change • Monotherapy • Trial termination • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

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