CytomX Therapeutics Clinical Programs Highlighted at American Society of Clinical Oncology ASCO20 Virtual Scientific Program
- First Presentation of Clinical Data for CX-2029, a Probody Drug Conjugate,
Directed Against CD71: A Previously Undruggable Target -
- Favorable Tolerability Profile Demonstrated for Anti-PD-L1 and Anti-CTLA-4 Probody Therapeutics -
- Data Updates for CX-2009 Support Phase 2 Investigations in Breast Cancer -
- Company to Host Webcast Today,
“A comprehensive body of evidence was presented today at ASCO 2020 that continues to validate our approach to conditional antibody activation and therapeutic target engagement with the Probody platform,” said
In the oral abstract 3502, Dr.
- Evidence of target lesion reduction was seen, principally in patients with tumors of squamous histology. (Figure 1)
° 3 confirmed partial responses were observed in 17 response-evaluable patients treated at doses ≥2 mg/kg of CX-2029, 2 in patients with squamous non-small cell lung cancer (SqNSCLC) and 1 in a patient with head and neck squamous cell cancer (HNSCC).
° 2 of the partial responses (both at the 3 mg/kg dose) were confirmed after the
April 20th cutoff date.
CX-2029 Waterfall Plot (Doses 2–5 mg/kg)
Figure 1 is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/51129ea3-a850-4d2f-9c41-4da88807669f
Safety Profile Supports Recommended Phase 2 Dose of 3 mg/kg, Every Three Weeks
- CX-2029 was generally well tolerated at doses up to 3 mg/kg.
- At doses of 0.25 – 5 mg/kg, CX-2029 circulated predominantly as the intact species (>90%).
- The most common treatment related adverse events (TRAE) were infusion related reactions, anemia, and neutropenia/leukopenia.
° Infusion related reactions were mostly Grade 1/2, occurred at the first dose, were not dose dependent and resolved upon initiation of supportive care.
° Hematologic TRAEs Grade ≥ 3 were dose dependent.
• Anemia and neutropenia are commonly observed with the MMAE payload.
• Anemia was managed with transfusions and supportive care.
- No CX-2029 treatment related deaths were reported and late onset Grade 3/4 TRAEs were predominately anemia and neutropenia.
- The etiology of anemia is under investigation and is likely multifactorial, including MMAE-related and CD71 expression on red blood cell precursors.
- CytomX is preparing to advance the dose of 3 mg/kg of CX-2029 administered every 3 weeks into 4 dose-expansion cohorts: HNSCC, SqNSCLC, esophageal carcinoma and diffuse large B cell lymphoma.
“Targeting CD71 with this novel approach has the potential to address areas of unmet medical need in difficult to treat tumor types, improving patient benefit,” said
CX-2009: Encouraging Clinical Activity Supports Advancement in HER2 Negative Breast Cancer
In Poster 18, Dr.
Durable Clinical Activity Observed in HER2 Negative (HER2-) Breast Cancer
- Evidence of target lesion reduction was observed at doses or dose equivalents of ≥4 mg/kg every 3 weeks across 68 evaluable patients including those with HER2- breast cancer, ovarian cancer, NSCLC and HNSCC.
° HER2- breast cancer patients were heavily pretreated with a median of 7 prior lines of therapy.
- 26 patients with HER2– breast cancer who received ≥4 mg/kg of CX-2009 were response-evaluable:
° 2 confirmed partial responses were observed, both in patients with hormone receptor positive (HR+) breast cancer.
° 3 unconfirmed responses were observed in patients with triple negative breast cancer (TNBC).
° Clinical benefit rates of 39% and 35% were observed at 16 and 24 weeks (CBR16 and CBR24, respectively).
• All 4 TNBC patients who achieved CBR16 also achieved CBR24.
CX-2009 Waterfall Plot and Spider Plot: HER2- Breast Cancer (≥4 mg/kg Every 3 Weeks)
Figure 2 is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/3d8523cb-3517-4ae7-b428-19700c46a749
Safety Profile Supports Recommended Phase 2 Dose of 7mg/kg, Every 3 Weeks
- CX-2009 was generally well tolerated at doses up to 7 mg/kg administered every three weeks.
- No dose limiting toxicities (DLTs) were reported at doses up to 7 mg/kg.
- DM4-related toxicities, including ocular, neuropathic, and hepatic were higher in frequency at dose equivalents greater than 7 mg/kg dosed at every three weeks compared to 7 mg/kg or lower.
° Occurrence and severity of ocular adverse events were dose dependent: One Grade 3+ event was observed in a patient treated at 5 mg/kg, none at 7 mg/kg.
° 20% of patients dosed at ≥8 mg/kg experienced Grade 3+ ocular adverse events.
- Preliminary pharmacokinetic (PK) data showed that CX-2009 circulates predominantly intact at all doses and PK is not strongly influenced by target-mediated drug disposition or anti-drug antibodies (ADAs). (Poster 329)
“Patients with advanced breast cancer continue to need treatment options, this is especially true for patients with hormone receptor positive and HER2 negative breast cancer that is refractory to hormonal based therapies,” said
CX-072: Anti-PD-L1 Probody Checkpoint Inhibitor
In the oral presentation of Abstract 3005 by Dr.
- As of an
April 20, 2020data cutoff, CX-072 monotherapy continued to demonstrate durable anti-tumor activity in patients with IO sensitive tumors such as TNBC, anal squamous cell carcinoma (aSCC), cutaneous squamous cell carcinoma (cSCC) and tumors with high mutational burden (hTMB).
- As of the same data cutoff, CX-072 in combination with ipilimumab had been administered to 27 patients with advanced solid tumors. Durable anti-cancer activity was observed including one complete response in a patient with aSCC who remains on study more than two years after first dose.
- Of the 141 patients across the monotherapy and combination arms: 34 patients received long term treatment in the monotherapy arm (median 11.3 months), and 6 patients received long term treatment in the combination arm (median 21.3 months).
- Grade 3/4 TRAEs were 10% and 5.9% for who received monotherapy < 6 months and ≥ 6 months, respectively, and 33% in each group in the combination arm.
- Long term patients experienced fewer irAEs and had no grade 3+ irAEs suggesting that tolerability early on can impact duration of treatment.
- Preliminary clinical PK data (Poster 332) and translational analyses of pre- and on-treatment biopsies (Poster 172) were supportive of the Probody mechanism of action.
CX-072 Monotherapy Waterfall Plots and Spider Plots (10 mg/kg)
Figure 3 is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/daf244be-f486-43cc-9cf1-b50b60a8dce9
BMS-986249: Anti-CTLA-4 Probody Demonstrates Encouraging Safety Profile in Phase 1 Trial
Bristol Myers Squibb presented dose escalation data from their Phase 1/2 trial of BMS-986249, a Probody version of the anti-CTLA-4 antibody ipilimumab in Abstract 3508. This trial assessed the safety, pharmacokinetics and pharmacodynamics of escalating doses of BMS-986249 as monotherapy or in combination with the anti PD-1 antibody nivolumab in patients with advanced cancers. The doses of BMS-986249 ranged from 240 mg to 2400 mg (approximately 3 - 30 mg/kg). BMS-986249 was generally well tolerated as monotherapy and in combination with nivolumab. Bristol Myers Squibb has initiated a randomized clinical trial to explore various doses of BMS-986249 in combination with nivolumab in patients with advanced melanoma.
ASCO20 Virtual Scientific Program - Posters and Presentations
Copies of the ASCO20 presentations and posters are available under the
Conference Call and Webcast
CytomX senior management will host a conference call and live webcast with slides today,
- From the CytomX website: http://ir.cytomx.com/events-and-presentations. Please access the website 15 minutes prior to the start of the call to download and install any necessary audio software.
- By telephone: Participants can access the call by dialing 1-877-809-6037 (
United States) or 1-615-247-0221 (International) referencing Conference ID 4267278.
- By replay: A replay of the webcast will be located under the Investor Relations section of CytomX’s website approximately two hours after the conclusion of the live call and will be available for 30 days following the call.
About CytomX Therapeutics
CytomX is a clinical-stage, oncology-focused biopharmaceutical company with a vision of transforming lives with safer, more effective therapies. We are developing a novel class of investigational antibody therapeutics, based on our Probody® technology platform, for the treatment of cancer.
Probody therapeutics are designed to remain inactive until they are activated by proteases in the tumor microenvironment. As a result, Probody therapeutics are intended to bind selectively to tumors and decrease binding to healthy tissue, to minimize toxicity and potentially create safer, more effective therapies. As leaders in the field, our innovative technology is designed to turn previously undruggable targets into druggable targets and to enable more effective combination therapies. CytomX and its partners, comprised of leading biotechnology and pharmaceutical companies, have developed a robust pipeline of potential first-in-class therapeutic candidates against novel, difficult to drug targets and potential best-in-class immunotherapeutic candidates against clinically validated targets. The CytomX clinical stage pipeline includes first-in-class product candidates against previously undruggable targets, including a CD166-targeting Probody drug conjugate wholly owned by CytomX (CX-2009) and a CD71-targeting Probody drug conjugate partnered with AbbVie (CX-2029). CD166 and CD71 are among cancer targets that are considered to be inaccessible to conventional antibody drug conjugates due to their presence on many healthy tissues. The CytomX clinical stage pipeline also includes cancer immunotherapeutic candidates against validated targets such as the CTLA-4-targeting Probody therapeutics, BMS-986249 and BMS-986288, partnered with Bristol Myers Squibb. CytomX has strategic drug discovery and development collaborations with AbbVie, Amgen, Astellas and Bristol Myers Squibb. For additional information about CytomX Therapeutics, visit www.cytomx.com and follow us on LinkedIn and Twitter.
CytomX Therapeutics Forward-Looking Statements